Publications by authors named "Earl G Noble"

44 Publications

White matter inflammation and cognitive function in a co-morbid metabolic syndrome and prodromal Alzheimer's disease rat model.

J Neuroinflammation 2020 Jan 21;17(1):29. Epub 2020 Jan 21.

Department of Anatomy & Cell Biology, Schulich School of Medicine & Dentistry, Western University, London, ON, N6A 5C1, Canada.

Background: Metabolic syndrome, the development of which is associated with high-caloric Western diet (HCD) intake, represent a risk factor for mild cognitive impairment (MCI) and dementia including Alzheimer's disease (AD) later in life. This study aimed to investigate the effect of diet-induced metabolic disturbances on white matter neuroinflammation and cognitive function in a transgenic (TG) Fischer 344 rat carrying a human β-amyloid precursor protein (APP) gene with Swedish and Indiana mutations (APP21 TG), a model of pre-AD and MCI.

Methods: TG and wildtype (WT) rats received either a HCD with 40% kJ from fat supplemented with 20% corn syrup drink or a standard diet for 12 weeks. Body weight, caloric intake, and blood pressure were measured repeatedly. End-point changes in glucose and lipid metabolism were also assessed. Open field task was used for assessment of activity; Morris water maze was used to assess spatial learning and memory. Cerebral white matter microglia and astrocytes, hippocampal neurons, and neuronal synapses were examined using immunohistochemistry.

Results: Rats maintained on the HCD developed significant obesity, visceral adiposity, dyslipidemia, and hyperinsulinemia, but did not become hypertensive. Impaired glucose tolerance was observed only in WT rats on the HCD. Total microglia number, activated OX-6+ microglia, as well as GFAP+ astrocytes located predominantly in the white matter were greater in the APP21 TG rat model in comparison to WT rats. HCD-driven metabolic perturbations further exacerbated white matter microgliosis and microglia cell activation in the APP21 TG rats and led to detectable changes in spatial reference memory in the comorbid prodromal AD and metabolic syndrome group compared to WT control rats. Neuronal density in the CA1 subregion of the hippocampus was not different between the experimental groups. Synaptic density in the CA1 and CA3 hippocampal subregions was lower in the TG rats compared to WT rats; however, there was no additional effect of the co-morbidity on this measure.

Conclusions: These results suggest that white matter neuroinflammation might be one of the possible processes of early interaction of metabolic syndrome with MCI and pre-AD and could be one of the early brain pathologies contributing to cognitive deficits observed in mild cognitive impairment and dementia, including AD cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-020-1698-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975033PMC
January 2020

Aerobic exercise training improves insulin-induced vasorelaxation in a vessel-specific manner in rats with insulin-treated experimental diabetes.

Diab Vasc Dis Res 2019 01 11;16(1):77-86. Epub 2018 Dec 11.

1 School of Kinesiology, Western University, London, ON, Canada.

Vascular insulin resistance often precedes endothelial dysfunction in type 1 diabetes mellitus. Strategies to limit vascular dysfunction include intensive insulin therapy (4-9 mM) and aerobic training. To avoid the risk of hypoglycaemia, individuals often prescribed conventional insulin therapy (9-15 mM) and participate in resistance training. In a model of type 1 diabetes mellitus, this study examined insulin-induced vasomotor function in the aorta and femoral artery to determine (1) whether resistance training with conventional insulin therapy provides the same benefits as aerobic training with conventional insulin therapy, (2) whether aerobic training or resistance training, when paired with conventional insulin therapy, results in superior vasomotor function compared to intensive insulin therapy alone and (3) whether vessel-specific adaptations exist. Groups consisted of conventional insulin therapy, intensive insulin therapy, aerobic training with conventional insulin therapy and resistance training with conventional insulin therapy. Following multiple low doses of streptozotocin, male Sprague-Dawley rats were supplemented with insulin to maintain blood glucose concentrations (9-15 mM: conventional insulin therapy, aerobic training and resistance training; 4-9 mM: intensive insulin therapy) for 12 weeks. Aerobic training performed treadmill exercise and resistance training consisted of weighted climbing. Coinciding with increased Akt signalling, aerobic training resulted in enhanced insulin-induced vasorelaxation in the femoral artery. Intensive insulin therapy displayed increased mitogen-activated protein kinase signalling and no improvement in insulin-stimulated vasorelaxation compared to all other groups. These data suggest that aerobic training may be more beneficial for limiting the pathogenesis of vascular disease in type 1 diabetes mellitus than merely intensive insulin therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1479164118815279DOI Listing
January 2019

Exercise Training Induced Cardioprotection with Moderate Hyperglycemia versus Sedentary Intensive Glycemic Control in Type 1 Diabetic Rats.

J Diabetes Res 2018 5;2018:8485624. Epub 2018 Jul 5.

Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, ON, Canada.

Intensive insulin therapy (IIT; 4-7 mmol/L) is the preferred treatment for type 1 diabetes mellitus (T1DM) patients to reduce the risk of cardiovascular disease (CVD). However, this treatment strategy has been questioned as it is accompanied with a sedentary lifestyle leading to weight gain and insulin resistance. T1DM patients who partake in high-intensity aerobic training (AT) to reduce CVD often utilize conventional insulin therapy (CIT; 9-15 mmol/L) to offset the risk of hypoglycemia. Moreover, exercise modalities incorporating resistance training (RT) have been shown to further reduce this risk. The purpose of this investigation was twofold: (1) to determine if CIT paired with AT results in larger cardioprotection from an ischemia-reperfusion (I-R) injury than IIT and (2) to establish if the integration of RT with AT (ART) results in similar cardioprotection as AT. Diabetic (D) male Sprague-Dawley rats were divided into D-IIT ( = 12), D-CIT ( = 12), D-AT ( = 8), D-RT ( = 8), and D-ART ( = 8). T1DM was induced with streptozotocin, and blood glucose was adjusted with insulin. D-AT occurred on a treadmill (27 m/min; 1 hr), D-RT performed weighted ladder climbs, and D-ART alternated daily between AT and RT. Exercise occurred 5 days/wk for 12 wks. This investigation demonstrates that cardioprotection following an I-R injury was similar between D-AT and D-IIT. This cardioprotection is not exercise-specific, and each provides unique advantages. D-AT leads to improved glycemia while insulin sensitivity was enhanced following resistance exercises. Thus, exercise is an effective means to elicit cardioprotection in T1DM. However, in addition to glycemia, other factors should be considered when tailoring an exercise program for T1DM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/8485624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079594PMC
December 2018

Effects of Ginseng Supplementation and Endurance-Exercise in the Artery-Specific Vascular Responsiveness of Diabetic and Sedentary Rats.

Front Physiol 2018 4;9:460. Epub 2018 May 4.

School of Kinesiology, University of Western Ontario, London, ON, Canada.

This study examined the effects of 12 weeks North-American ginseng supplementation, exercise training, and sedentary behavior on vascular responses in type I diabetic rats. The following hypotheses were tested: (1) ginseng supplementation would result in improved vascular responsiveness and sensitivity; (2) exercise training would result in further improvement in these vascular responses; (3) control rats with no access to exercise would show a depressed vascular response compared to control rats that were not exposed to a sedentary lifestyle. Groups: non-diabetic sedentary control (C), sedentary diabetic (D), sedentary diabetic with ginseng supplementation (D+GS), diabetic with ginseng supplementation and high-intensity endurance exercise (D+GS+EX), and control not exposed to sedentary behavior (C). Diabetes was induced by streptozotocin. Arteries were excised, cleaned, and mounted onto a myography system. Percent vasorelaxation to acetylcholine (ACh) (10 M ACh to 10 M ACh) of the carotid artery was similar in C (57 ± 31%), C (66 ± 35%), D (58 ± 36%), D+GS+Ex (71 ± 37%), and D+GS (64 ± 37%) ( > 0.05). Percent vasorelaxation of the aorta was smaller in C (23 ± 17%) compared to C (46 ± 35%), D (60 ± 40%), D+GS+Ex (64 ± 40%), and D+GS (56 ± 39%) ( < 0.05), and smaller in C compared to D+GS+Ex ( < 0.05). In the femoral, the percent vasorelaxation was reduced in D (18 ± 16%) compared to all the other conditions (C, 43 ± 22%; C, 79 ± 28%; D+GS+Ex, 55 ± 27%; D+GS, 45 ± 26%; < 0.05), but larger in C compared to the other conditions (C, D, D+GS+Ex, D+GS; < 0.05). Diabetes and sedentary lifestyle have detrimental effects on vascular responses that are evident in the femoral arteries of the diabetic rats. Ginseng supplementation restored the loss of sensitivity, with no added vascular protection of exercise training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2018.00460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946630PMC
May 2018

Effect of Combined Exercise Versus Aerobic-Only Training on Skeletal Muscle Lipid Metabolism in a Rodent Model of Type 1 Diabetes.

Can J Diabetes 2018 Aug 6;42(4):404-411. Epub 2017 Dec 6.

Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada. Electronic address:

Objectives: Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 1 diabetes. Although lipid metabolism is restored with aerobic exercise training, the risk for postexercise hypoglycemia is increased with this modality. Integrating resistance and aerobic exercise is associated with reduced hypoglycemic risk; however, the effects of this exercise modality on lipid metabolism and insulin resistance remain unknown. We compared the effects of combined (aerobic + resistance) versus aerobic exercise training on oxidative capacity and muscle lipid metabolism in a rat model of type 1 diabetes.

Methods: Male Sprague-Dawley rats were divided into 4 groups: sedentary control (C), sedentary control + diabetes (CD), diabetes + high-intensity aerobic exercise (DAE) and diabetes + combined aerobic and resistance exercise (DARE). Following diabetes induction (20 mg/kg streptozotocin over five days), DAE rats ran for 12 weeks (5 days/week for 1 hour) on a motorized treadmill (27 m/min at a 6-degree grade), and DARE rats alternated daily between running and incremental weighted ladder climbing.

Results: After training, DAE showed reduced muscle CD36 protein content and lipid content compared to CD (p≤0.05). DAE rats also had significantly increased citrate synthase (CS) activity compared to CD (p≤0.05). DARE rats showed reduced CD36 protein content compared to CD and increased CS activity compared to CD and DAE rats (p≤0.05). DARE rats demonstrated increased skeletal muscle lipid staining, elevated lipin-1 protein content and insulin sensitivity (p≤0.05).

Conclusions: Integration of aerobic and resistance exercise may exert a synergistic effect, producing adaptations characteristic of the "athlete's paradox," including increased capacity to store and oxidize lipids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcjd.2017.09.013DOI Listing
August 2018

Aerobic Endurance Training Does Not Protect Bone Against Poorly Controlled Type 1 Diabetes in Young Adult Rats.

Calcif Tissue Int 2017 04 21;100(4):374-381. Epub 2017 Jan 21.

School of Dietetics and Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Ste-Anne-de-Bellevue, QC, H9X 2E3, Canada.

Streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) decreases trabecular bone volume and bone strength in rodents. The current study investigated the potential protective effects of aerobic endurance training (AET) on bone in STZ-induced T1DM young adult rats. Sixty-four 8-week-old male Sprague-Dawley rats were randomly divided into 4 groups of 16: control non-T1DM sedentary (CS) and exercised (CX), T1DM sedentary (DS) and exercised (DX). Blood glucose was maintained at 9-15 mmol/L using subcutaneously implanted insulin pellets (Linplant, Linshin Canada, Inc.). AET was performed at ~75-85% VO for 1 h/day, 5 day/week for 10 weeks. Areal and volumetric bone mineral density (aBMD and vBMD; excised femur) were measured using dual-energy X-ray absorptiometry (DXA; QDR 4500A) and micro computed tomography (μCT; Aloka). Bone strength was tested using a 3-point bending test (Instron 5544 Load Frame). Two-way ANOVA was used to test for T1DM and exercise differences followed by Tukey's HSD tests for interaction effects; significance was set at P < 0.05. T1DM had lower body weight (18.0%), aBMD (8.6%), cortical vBMD (1.6%), trabecular vBMD (2.1%), maximum load at break (22.2%), and increased elastic modulus (11.3%) vs. control (P < 0.001). Exercise in T1DM further decreased body weight (4.7%) vs. sedentary (P = 0.043) and maximum extension during the bending test that demonstrated DX was increased (7.3%) vs. CX (P = 0.033). There were no other beneficial effects of exercise on bone. These results suggest that 10 weeks of AET in rats do not have protective effects on bone in the short term and that T1DM rats have compromised bone health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00223-016-0227-2DOI Listing
April 2017

Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.

Sci Rep 2016 05 20;6:26379. Epub 2016 May 20.

Exercise Biochemistry Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.

The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep26379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873835PMC
May 2016

The glucoregulatory response to high-intensity aerobic exercise following training in rats with insulin-treated type 1 diabetes mellitus.

Appl Physiol Nutr Metab 2016 Jun 10;41(6):631-9. Epub 2016 Feb 10.

a School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, ON, Canada.

An acute bout of exercise elicits a rapid, potentially deleterious, reduction in blood glucose in patients with type 1 diabetes mellitus (T1DM). In the current study, we examined whether a 10-week aerobic training program could alleviate the rapid exercise-associated reduction in blood glucose through changes in the glucoregulatory hormonal response or increased hepatic glycogen storage in an insulin-treated rat model of T1DM. Thirty-two male Sprague-Dawley rats were divided evenly into 4 groups: non-T1DM sedentary (C) (n = 8), non-T1DM exercised (CX) (n = 8), T1DM sedentary (D) (n = 8), and T1DM exercised (DX) (n = 8). Exercise training consisted of treadmill running for 5 days/week (1 h, 27 m/min, 6% grade) for 10 weeks. T1DM was induced by multiple streptozotocin injections (20 mg/kg) followed by implantation of subcutaneous insulin pellets. At week 1, an acute exercise bout led to a significant reduction in blood glucose in DX (p < 0.05), whereas CX exhibited an increase in blood glucose (p < 0.05). During acute exercise, serum epinephrine was increased in both DX and CX (p < 0.05), whereas serum glucagon was increased during recovery only in CX (p < 0.01). Following aerobic training in DX, the exercise-mediated reduction in blood glucose remained; however, serum glucagon increased to the same extent as in CX (p < 0.05). DX exhibited significantly less hepatic glycogen (p < 0.001) despite elevations in glycogenic proteins in the liver (p < 0.05). Elevated serum epinephrine and decreased hepatic adrenergic receptor expression were also evident in DX (p < 0.05). In summary, despite aerobic training in DX, abrupt blood glucose reductions and hepatic glycogen deficiencies were evident. These data suggest that sympathetic overactivity may contribute to deficiencies in hepatic glycogen storage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/apnm-2015-0558DOI Listing
June 2016

High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia.

J Diabetes Res 2016 18;2016:8164518. Epub 2016 Jan 18.

Exercise Biochemistry Laboratory, School of Kinesiology, Faculty of Health Sciences, Western University, London, ON, Canada N6A 3K7.

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9-17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2016/8164518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4739461PMC
December 2016

Effects of Two Different Weight Training Programs on Swimming Performance and Muscle Enzyme Activities and Fiber Type.

J Strength Cond Res 2016 Feb;30(2):305-10

School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada.

The effects of 2 different weight training programs incorporating bench press (BP) and pullover (PO) exercises on swimming performance, power, enzyme activity, and fiber type distribution were studied on 16 men (age = 23 ± 4 years). A 30-second group (n = 6) performed up to 20 repetitions of BP and PO in 30 seconds. The 2-minute group (n = 6) performed a maximum of 80 repetitions of BP and PO in 2 minutes. As participants reached the prescribed 20 or 80 repetitions, the weight was increased 4.5 kg. A third group (n = 4) served as nontraining controls. Exercise groups trained 3 times per week for 6 weeks. Maximal effort swims of 50 and 200 yd were performed before and after training. Training resulted in increases in work on both exercises in both groups pre- to post-training (BP 30 seconds, 722 ± 236-895 ± 250 kg; PO 30 seconds, 586 ± 252-1,090 ± 677 kg; and BP 2 minutes, 1,530 ± 414-1,940 ± 296; PO 2 minutes, 1,212 ± 406-2,348 ± 194, p ≤ 0.05). Swim performances of the 30-second group improved for both the 50-yd (32.0 ± 6.9 seconds, 30.0 ± 5.9 seconds, p ≤ 0.05) and 200-yd swims 200.0 ± 54 seconds, 182 ± 45.1 seconds (p ≤ 0.05), whereas 2-minute training improved only the 200-yd swim (198.3 ± 32.3 seconds, 186.2 ± 32.2 seconds). No changes in swim performance were observed for the control group. Triceps muscle succinate dehydrogenase activities increased (pre 3.48 ± 1.1 μmol · g(-1) wet weight per minute, post 6.25 ± 1.5 μmoles · g(-1) wet weight per minute, p ≤ 0.05) in only the 30-second training group, whereas phosphofructokinase activities and fiber type distribution did not change in either training group. This study has demonstrated that a 30-second 20-repetition weight training program, specific to the swimming musculature without concurrent swim training, improves swimming performances at both 50- and 200-yd distances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1519/JSC.0000000000000842DOI Listing
February 2016

North American ginseng protects against muscle damage and reduces neutrophil infiltration after an acute bout of downhill running in rats.

Appl Physiol Nutr Metab 2015 Feb 10;40(2):116-21. Epub 2014 Oct 10.

a School of Kinesiology, The University of Western Ontario, London, ON N6A 3K7, Canada.

Eccentric muscle contractions such as those experienced during downhill running are associated with inflammation, delayed-onset of muscle soreness, myofiber damage, and various functional deficits. North American ginseng (Panax quinquefolius L.) has been reported to possess anti-inflammatory properties and thus may offset some of this exercise-induced damage. Hence, we tested the hypothesis that intervention with North American ginseng would reduce eccentric exercise-induced muscle damage and inflammation. Male Wistar rats were fed (300 mg/(kg·day)(-1)) of either an alcohol (AL) or aqueous (AQ) extract of North American ginseng for 14 days before a single bout of downhill running and were compared with matching nonexercised (C) groups. Plasma creatine kinase levels were significantly reduced in both ginseng treated groups compared with the C group that received a water placebo (p < 0.002). Further, the AQ but not AL group also showed attenuated morphological signs of damage (hemotoxylin and eosin) as well as reduced levels of infiltrating neutrophils (HIS48) in the soleus muscle (p < 0.001). In summary, supplementation with an AQ but not AL extract of North American ginseng was able to reduce eccentric exercise-induced muscle damage and inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/apnm-2014-0331DOI Listing
February 2015

Morphological assessment of pancreatic islet hormone content following aerobic exercise training in rats with poorly controlled Type 1 diabetes mellitus.

Islets 2014 ;6(2):e29221

a School of Kinesiology; Faculty of Health Sciences; University of Western Ontario; London, ON Canada.

Regular exercise has been shown to improve many complications of Type 1 diabetes mellitus (T1DM) including enhanced glucose tolerance and increased cardiac function. While exercise training has been shown to increase insulin content in pancreatic islets of rats with T1DM, experimental models were severely hyperglycemic and not undergoing insulin treatment. Further, research to date has yet to determine how exercise training alters glucagon content in pancreatic islets. The purpose of the present investigation was to determine the impact of a 10-week aerobic training program on pancreatic islet composition in insulin-treated rats with T1DM. Second, it was determined whether the acute, exercise-mediated reduction in blood glucose experienced in rats with T1DM would become larger in magnitude following aerobic exercise training. Diabetes was induced in male Sprague-Dawley rats by multiple low dose injections of streptozotocin (20mg/kg i.p.) and moderate intensity aerobic exercise training was performed on a motorized treadmill for one hour per day for a total of 10 weeks. Rats with T1DM demonstrated significantly less islet insulin, and significantly more islet glucagon hormone content compared with non-T1DM rats, which did not significantly change following aerobic training. The reduction in blood glucose in response to a single exercise bout was similar across 10 weeks of training. Results also support the view that different subpopulations of islets exist, as small islets (<50 μm diameter) had significantly more insulin and glucagon in rats with and without T1DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4161/isl.29221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4594201PMC
August 2015

Ischemia-reperfusion injury and hypoglycemia risk in insulin-treated T1DM rats following different modalities of regular exercise.

Physiol Rep 2014 Nov 20;2(11). Epub 2014 Nov 20.

School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada Health and Rehabilitation Sciences, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada.

While regular exercise is known to improve cardiovascular function, individuals with type 1 diabetes mellitus (T1DM) have an increased risk for exercise-induced hypoglycemia. Clinical data suggest that higher intensities of acute exercise may alleviate the onset of hypoglycemia; however, the cardiovascular benefit from these forms of exercise in patients with T1DM has yet to be established. The purpose of this study was to investigate the cardiovascular benefit of different regular exercise regimes, while monitoring blood glucose concentrations during the post-exercise period. Fifty rats (8-week-old Sprague-Dawley male) were equally divided into the following groups: nondiabetic sedentary (C), diabetic sedentary (DS), diabetic low-intensity aerobic exercise (DL), diabetic high-intensity aerobic exercise (DH) or diabetic resistance exercise (DR). Diabetes was induced using multiple streptozotocin injections (5×; 20 mg/kg) while subcutaneous insulin pellets maintained glycemia in a range typical for individuals that exercise with T1DM. Exercise consisted of six weeks of treadmill running (DL and DH) or weighted ladder climbs (DR). The cardiovascular benefit of each exercise program was determined by the myocardial recovery from ischemia-reperfusion injury. Exercise-related cardiovascular protection was dependent on the exercise modality, whereby DH demonstrated the greatest protection following an ischemic-reperfusion injury. Each exercise modality caused a significant decline in blood glucose in the post-exercise period; however, blood glucose levels did not reach hypoglycemic concentrations (<3.0 mmol/L) throughout the exercise intervention. These results suggest that elevating blood glucose concentrations prior to exercise allows patients with T1DM to perform exercise that is beneficial to the myocardium without the accompanying risk of hypoglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.12201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255808PMC
November 2014

The relationship between blood pressure and sciatic nerve blood flow velocity in rats with insulin-treated experimental diabetes.

Diab Vasc Dis Res 2014 Jul 22;11(4):281-289. Epub 2014 May 22.

Neurovascular Research Laboratory, School of Kinesiology, Western University, London, ON, Canada Department of Physiology and Pharmacology, Western University, London, ON, Canada

Peripheral nerve blood flow (NBF) does not autoregulate but, instead, responds passively to changes in mean arterial pressure (MAP). How this relationship is impacted by insulin-treated experimental diabetes (ITED) is unknown. We tested the hypothesis that ITED will reduce NBF across a range of MAP in Sprague Dawley rats. Following 10 weeks of control or ITED conditions, conscious MAP (tail-cuff) was measured, and under anaesthesia, the MAP (carotid artery catheter, pressure transducer) and NBF (Doppler ultrasound, 40 MHz) responses to sodium nitroprusside (60 µg/kg) and phenylephrine (12 µg/kg) infusion were recorded (regression equations for MAP vs NBF were created for each rodent). Thereafter, motor nerve conduction velocity (MNCV) and nerve vascularization (haematoxylin and eosin stain) were determined. Conscious MAP was higher and MNCV was lower in the ITED group (p < 0.01). In response to drug infusions, the ΔMAP and ΔNBF were similar between groups (p ≥ 0.18). Estimated conscious NBF (based on substituting conscious MAP values into each individual regression equation) was greater in the ITED group (p < 0.01). Sciatic nerve vascularization was similar between groups (p ≥ 0.50). In contrast to the hypothesis, NBF was not reduced across a range of MAP. In spite of increased estimated conscious NBF values, MNCV was reduced in rats with ITED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1479164114533357DOI Listing
July 2014

Exercise training enhances insulin-stimulated nerve arterial vasodilation in rats with insulin-treated experimental diabetes.

Am J Physiol Regul Integr Comp Physiol 2014 Jun 16;306(12):R941-50. Epub 2014 Apr 16.

Neurovascular Research Laboratory, School of Kinesiology, The University of Western Ontario, London, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada

Insulin stimulates nerve arterial vasodilation through a nitric oxide (NO) synthase (NOS) mechanism. Experimental diabetes reduces vasa nervorum NO reactivity. Studies investigating hyperglycemia and nerve arterial vasodilation typically omit insulin treatment and use sedentary rats resulting in severe hyperglycemia. We tested the hypotheses that 1) insulin-treated experimental diabetes and inactivity (DS rats) will attenuate insulin-mediated nerve arterial vasodilation, and 2) deficits in vasodilation in DS rats will be overcome by concurrent exercise training (DX rats; 75-85% VO2 max, 1 h/day, 5 days/wk, for 10 wk). The baseline index of vascular conductance values (VCi = nerve blood flow velocity/mean arterial blood pressure) were similar (P ≥ 0.68), but peak VCi and the area under the curve (AUCi) for the VCi during a euglycemic hyperinsulinemic clamp (EHC; 10 mU·kg(-1)·min(-1)) were lower in DS rats versus control sedentary (CS) rats and DX rats (P ≤ 0.01). Motor nerve conduction velocity (MNCV) was lower in DS rats versus CS rats and DX rats (P ≤ 0.01). When compared with DS rats, DX rats expressed greater nerve endothelial NOS (eNOS) protein content (P = 0.04). In a separate analysis, we examined the impact of diabetes in exercise-trained rats alone. When compared with exercise-trained control rats (CX), DX rats had a lower AUCi during the EHC, lower MNCV values, and lower sciatic nerve eNOS protein content (P ≤ 0.03). Therefore, vasa nervorum and motor nerve function are impaired in DS rats. Such deficits in rats with diabetes can be overcome by concurrent exercise training. However, in exercise-trained rats (CX and DX groups), moderate hyperglycemia lowers vasa nervorum and nerve function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpregu.00508.2013DOI Listing
June 2014

American ginseng acutely regulates contractile function of rat heart.

Front Pharmacol 2014 14;5:43. Epub 2014 Mar 14.

School of Kinesiology, Faculty of Health Sciences, Western University London, ON, Canada ; Ontario Ginseng Innovation and Research Consortium London, ON, Canada.

Chronic ginseng treatments have been purported to improve cardiac performance. However reports of acute administration of ginseng on cardiovascular function remain controversial and potential mechanisms are not clear. In this study, we examined the effects of acute North American ginseng (Panax quinquefolius) administration on rat cardiac contractile function by using electrocardiogram (ECG), non-invasive blood pressure (BP) measurement, and Langendorff isolated, spontaneously beating, perfused heart measurements (LP). Eight-week old male Sprague-Dawley rats (n = 8 per group) were gavaged with a single dose of water-soluble American ginseng at 300 mg/kg body weight. Heart rate (HR) and BP were measured prior to and at 1 and 24 h after gavaging (ECG and BP). Additional groups were used for each time point for Langendorff measurements. HR was significantly decreased (ECG: 1 h: 6 ± 0.2%, 24 h: 8 ± 0.3%; BP: 1 h: 8.8 ± 0.2%, 24 h: 13 ± 0.4% and LP: 1 h: 22 ± 0.4%, 24 h: 19 ± 0.4%) in rats treated with water-soluble ginseng compared with pre or control measures. An initial marked decrease in left ventricular developed pressure was observed in LP hearts but BP changes were not observed in BP group. A direct inhibitory effect of North American ginseng was observed on cardiac contractile function in LP rats and on fluorescence measurement of intracellular calcium transient in freshly isolated cardiac myocytes when exposed to ginseng (1 and 10 μg/ml). Collectively these data present evidence of depressed cardiac contractile function by acute administration of North American ginseng in rat. This acute reduction in cardiac contractile function appears to be intrinsic to the myocardium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2014.00043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953749PMC
March 2014

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

Metabolism 2013 Oct 28;62(10):1485-94. Epub 2013 Jun 28.

Health and Rehabilitation Sciences, University of Western Ontario, London, Ontario, Canada.

Unlabelled: Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content.

Objective: To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats.

Methods: Fifty rats were divided into 5 groups; control, diabetic control, diabetic resistance exercised, and diabetic high and low intensity treadmill exercised. Diabetes was induced using multiple low dose Streptozotocin (20 mg/kg/day) injections and blood glucose concentrations were maintained moderately hyperglycemic through subcutaneous insulin pellets. Resistance trained rats climbed a ladder with incremental loads, while treadmill trained rats ran on a treadmill at 27 or 15 m/min, respectively, all for 6 weeks.

Results: At weeks 3 and 6, area under the curve measurements following an intravenous glucose tolerance test (AUC-IVGTT) in all diabetic groups were higher than control rats (p<0.05). At 6 weeks, all exercise groups had significantly lower AUC-IVGTT values than diabetic control animals (p<0.05). Treadmill trained rats had the lowest insulin dose requirement of the T1DM rats and the greatest reduction in insulin dosage was evident in high intensity treadmill exercise. Concomitant with improvements in glucose handling improvements, tissue-specific elevations in GLUT4 content were demonstrated in both red and white portions of vastus lateralis and gastrocnemius muscles, suggesting that glucose handling capacity was altered in the skeletal muscle of exercised T1DM rats.

Conclusions: These results suggest that, while all exercise modalities can improve glucose tolerance, each mode leads to differential improvements in insulin requirements and protein content alterations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2013.05.012DOI Listing
October 2013

Glucose-stimulated insulin secretion causes an insulin-dependent nitric oxide-mediated vasodilation in the blood supply of the rat sciatic nerve.

Am J Physiol Regul Integr Comp Physiol 2013 Jul 24;305(2):R157-63. Epub 2013 Apr 24.

Neurovascular Research Laboratory, School of Kinesiology, Western University, London, Ontario, Canada.

This study tested the hypothesis that acute hyperglycemia reduces sciatic nerve blood flow in Sprague-Dawley rats. Anesthetized rats underwent cannulation of their right jugular vein (for anesthetic/nutrient/drug infusion) and right carotid artery (for continuous blood pressure measurement via pressure transducer). The left sciatic nerve was exposed and nerve blood velocity (NBV) was assessed from an arterial segment lying superficially along the sciatic nerve (Doppler ultrasound, 40 MHz). NBV and mean arterial pressure (MAP) values were collected, and an index of nerve vascular conductance (NVC) was established (NBV/MAP) at baseline and at 5, 10, 20, and 30 min (and 80 min for insulin) following 1) low glucose infusion, 1 g/kg (50% solution); 2) high glucose infusion, 3 g/kg; 3) high glucose infusion in the absence of a functioning pancreas; 4) euglycemic hyperinsulinemic clamp-insulin infusion (10 mU·kg⁻¹·min⁻¹; 0.4 IU/ml); 5) high glucose infusion + NG-nitro-L-arginine methyl ester (L-NAME) infusion (30 mg/kg); and 6) L-NAME alone followed 20 min later by high glucose infusion. High glucose infusion increased NVC by ~120% relative to baseline (P < 0.001), and this dilation was attenuated in rats without a functioning pancreas (i.e., without insulin secretion) (P = 0.004) and following L-NAME infusion (P = 0.011). Therefore, the vasodilation in rat sciatic nerve during glucose infusion was dependent upon the insulin response and acted through a nitric oxide synthase pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpregu.00095.2013DOI Listing
July 2013

High-intensity endurance training results in faster vessel-specific rate of vasorelaxation in type 1 diabetic rats.

PLoS One 2013 19;8(3):e59678. Epub 2013 Mar 19.

School of Kinesiology, Western University, London, Ontario, Canada.

This study examined the effects of 6 weeks of moderate- (MD) and high-intensity endurance training (HD) and resistance training (RD) on the vasorelaxation responsiveness of the aorta, iliac, and femoral vessels in type 1 diabetic (D) rats. Vasorelaxation to acetylcholine was modeled as a mono-exponential function. A potential mediator of vasorelaxation, endothelial nitric oxide synthase (e-NOS) was determined by Western blots. Vessel lumen-to-wall ratios were calculated from H&E stains. The vasorelaxation time-constant (τ) (s) was smaller in control (C) (7.2 ± 3.7) compared to D (9.1 ± 4.4) and it was smaller in HD (5.4 ± 1.5) compared to C, D, RD (8.3 ± 3.7) and MD (8.7 ± 3.8) (p<0.05). The rate of vasorelaxation (% · s(-1)) was larger in HD (2.7 ± 1.2) compared to C (2.0 ± 1.2), D (2.0 ± 1.5), RD (2.0 ± 1.0), and MD (2.0 ± 1.2) (p<0.05). τ vasorelaxation was smaller in the femoral (6.9 ± 3.7) and iliac (6.9 ± 4.7) than the aorta (9.0 ± 5.0) (p<0.05). The rate of vasorelaxation was progressively larger from the femoral (3.1 ± 1.4) to the iliac (2.0 ± 0.9) and to the aorta (1.3 ± 0.5) (p<0.05). e-NOS content (% of positive control) was greater in HD (104 ± 90) compared to C (71 ± 64), D (85 ± 65), RD (69 ± 43), and MD (76 ± 44) (p<0.05). e-NOS normalized to lumen-to-wall ratio (% · mm(-1)) was larger in the femoral (11.7 ± 11.1) compared to the aorta (3.2 ± 1.9) (p<0.05). Although vasorelaxation responses were vessel-specific, high-intensity endurance training was the most effective exercise modality in restoring the diabetes-related loss of vascular responsiveness. Changes in the vasoresponsiveness seem to be endothelium-dependent as evidenced by the greater e-NOS content in HD and the greater normalized e-NOS content in the smaller vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0059678PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602035PMC
September 2013

Acute endurance exercise induces changes in vasorelaxation responses that are vessel-specific.

Am J Physiol Regul Integr Comp Physiol 2013 Apr 13;304(7):R574-80. Epub 2013 Feb 13.

School of Kinesiology, London, Ontario, Canada.

The dynamic adjustment and amplitude of the endothelium-dependent vasorelaxation of the carotid, aorta, iliac, and femoral vessels were measured in response to acute low- (LI) or high-intensity (HI) endurance exercise. Vasorelaxation to 10(-4) M ACh was evaluated in 10 control, 10 LI, and 10 HI rats. Two-millimeter sections of carotid, aorta, iliac, and femoral arteries were mounted onto a myography system. Vasorelaxation responses were modeled as a monoexponential function. The overall τ (control, 10.5 ± 6.0 s; LI, 10.4 ± 5.7 s; HI, 11.0 ± 6.9 s) and time-to-steady-state (control, 47.6 ± 24.0 s; LI, 46.2 ± 22.8 s; HI, 49.1 ± 28.3 s) was similar in LI, HI, and control (P > 0.05). The overall (average of four vessel-type) % vasorelaxation was larger in LI (73 ± 16%) and HI (73 ± 16%) than in control (66 ± 19%) (P < 0.05). The overall rate of vasorelaxation was greater in LI (1.9 ± 0.9%·s(-1)) and HI (1.9 ± 1.1%·s(-1)) compared with control (1.6 ± 0.7%·s(-1)) (P < 0.05). The vessel-specific responses (average response for the three conditions) showed that carotid displayed a slower adjustment (τ, 18.9 ± 4.4 s; time-to-steady-state, 80.4 ± 18.4 s) compared with the aorta (τ, 10.3 ± 3.8 s; time-to-steady-state, 46.3 ± 15.2 s), the iliac (τ, 6.3 ± 2.1 s; time-to-steady-state, 30.3 ± 9.0 s), and the femoral (τ, 6.0 ± 1.9 s; time-to-steady-state, 29.3 ± 8.4 s). The % vasorelaxation was larger in the carotid (82 ± 14%) than in the aorta (67 ± 16%), iliac (61 ± 13%), and femoral (71 ± 19%) (P > 0.05). The rate of vasorelaxation was carotid (1.1 ± 0.2%·s(-1)), aorta (1.5 ± 0.4%·s(-1)), iliac (2.2 ± 0.8%·s(-1)), and femoral (2.6 ± 1.0%·s(-1)). In conclusion, an acute bout of endurance exercise increased vascular responsiveness. The dynamic and percent adjustments were vessel-specific with vessel function likely determining the response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpregu.00508.2012DOI Listing
April 2013

Impact of exercise and metabolic disorders on heat shock proteins and vascular inflammation.

Autoimmune Dis 2012 17;2012:836519. Epub 2012 Dec 17.

School of Kinesiology, University of Western Ontario, London, ON, Canada.

Heat shock proteins (Hsp) play critical roles in the body's self-defense under a variety of stresses, including heat shock, oxidative stress, radiation, and wounds, through the regulation of folding and functions of relevant cellular proteins. Exercise increases the levels of Hsp through elevated temperature, hormones, calcium fluxes, reactive oxygen species (ROS), or mechanical deformation of tissues. Isotonic contractions and endurance- type activities tend to increase Hsp60 and Hsp70. Eccentric muscle contractions lead to phosphorylation and translocation of Hsp25/27. Exercise-induced transient increases of Hsp inhibit the generation of inflammatory mediators and vascular inflammation. Metabolic disorders (hyperglycemia and dyslipidemia) are associated with type 1 diabetes (an autoimmune disease), type 2 diabetes (the common type of diabetes usually associated with obesity), and atherosclerotic cardiovascular disease. Metabolic disorders activate HSF/Hsp pathway, which was associated with oxidative stress, increased generation of inflammatory mediators, vascular inflammation, and cell injury. Knock down of heat shock factor-1 (HSF1) reduced the activation of key inflammatory mediators in vascular cells. Accumulating lines of evidence suggest that the activation of HSF/Hsp induced by exercise or metabolic disorders may play a dual role in inflammation. The benefits of exercise on inflammation and metabolism depend on the type, intensity, and duration of physical activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2012/836519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533452PMC
January 2013

Vessel-specific rate of vasorelaxation is slower in diabetic rats.

Diab Vasc Dis Res 2013 Mar 4;10(2):179-86. Epub 2012 Sep 4.

School of Kinesiology, Western University, London, ON, Canada.

The rate of adjustment of endothelium-dependent vasorelaxation was examined in the aorta, iliac and femoral arteries of eight control and eight diabetic rats with and without supplementation with vitamin C. Vessels were constricted using 10(-5) M phenylephrine (PE) and relaxed with 10(-4) M acetylcholine (ACh condition) or 10(-4) M ACh plus 10(-4) M vitamin C (ACh + vitamin C condition) in a myography system. Vasorelaxation was modelled as a mono-exponential function using a non-linear regression analysis. The adjustment (τ) of vasorelaxation was faster in control (6.6 ± 3.2 s) compared to diabetic rats (8.4 ± 3.4 s) (p < 0.05). The time-to-steady-state tended to be shorter in control (32.0 ± 13.9 s) compared to diabetic rats (38.0 ± 15.0 s) (p = 0.1). ACh + vitamin C did not speed the vasorelaxation response. The τ for vasorelaxation was shorter in the femoral (6.5 ± 2.7 s) and iliac (6.8 ± 2.5 s) compared to the aorta (9.2 ± 4.2 s) (p < 0.05). The rate of vasorelaxation was greater in the femoral (3.2 ± 1.4%·s(-1)) compared to the iliac (2.0 ± 1.0%·s(-1)) and aorta (1.1 ± 0.4%·s(-1)) in both groups and in the iliac compared to the aorta (p < 0.05) in the control group. In conclusion, the vasorelaxation response was vessel specific with a slower rate of adjustment in diabetic compared to control animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1479164112454758DOI Listing
March 2013

Core temperature is a greater influence than endogenous 17β-estradiol on the exercise-induced accumulation of myocardial heat shock protein mRNA.

Can J Physiol Pharmacol 2011 Nov 1;89(11):855-60. Epub 2011 Nov 1.

a School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario London, ON N6A 3K7, Canada.

Female rats typically do not show significant increases in myocardial Hsp70 after exercise unless trained (exercise over days or weeks). 17β-Estradiol (E2) has been linked to this inhibition, but it varies considerably over the rodent estrus cycle. Consequently, we examined whether the inhibitory effects of endogenously produced E2 (measured immediately pre-exercise) were acute in exercised female Sprague-Dawley rats (60 min treadmill running at 30 m·min(-1)). Myocardial hsp70-1 and hsp70-2 mRNA were measured 30 min post-exercise, and their expression was inversely correlated with pre-exercise plasma Ε2 ( hsp70-1 mRNA, r(2) = 0.308, p = 0.011; hsp70-2 mRNA, r(2) = 0.238, p = 0.029). However, hsp70-1 and hsp70-2 mRNA exhibited much stronger correlations with core temperature achieved during exercise (r(2) = 0.812, p = 0.000; and r(2) = 0.738, p = 0.000, respectively). Consequently, although endogenous Ε2 in gonadally intact female rats may attenuate myocardial hsp70 mRNA accumulation, suggesting a reason why training maximizes this response in females, core temperature during exercise is still a greater stimulus to this response.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/y11-089DOI Listing
November 2011

hsp70 mRNA temporal localization in rat skeletal myofibers and blood vessels post-exercise.

Cell Stress Chaperones 2012 Jan 28;17(1):109-20. Epub 2011 Sep 28.

School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, ON N6A 3K7, Canada.

Rapid transcription of the survival transcript, inducible heat shock protein 70 (hsp70), is critical for mounting cytoprotection against severe cellular stress, like elevated temperature. Previous investigations have demonstrated that exercise-induced expression of Hsp70 protein occurs in a fiber-specific pattern; however, the activation pattern of hsp70 mRNA expression remains unclear in skeletal muscle. Consequentially, the temporal localization of hsp70 mRNA was characterized via in situ hybridization (ISH) experiments examining fast-muscle, white vastus: 1, 3, 10, and 24 h after a single bout of intense treadmill running (1 h, 30 m/min, 6% grade) in rats. The role that the physiologic temperature stress associated with exercise (raising core body temperature to 40.0°C for 15 min (HS-40.0°C)) might play in inducing hsp70 mRNA expression was also explored. In skeletal muscle myofibers (SkM), hsp70 mRNA ISH signal was observed to be concentrated in a punctate manner that was associated with nuclei post-exercise. HS-40°C treatment produced minimal detectable hsp70 mRNA ISH signal in SkM. In large intermyofibrillar blood vessels (BV), peak hsp70 mRNA signal, distributed throughout the vessel wall, was observed 1 h post-exercise. In BV, no differences in hsp70 mRNA signal were observed between HS-40°C and EX-1 h. Results indicate that the majority of hsp70 mRNA is retained in a perinuclear localization in SkM post-exercise. They further suggest a muscle-type specific time course for peak hsp70 mRNA expression. This investigation suggests that the physiologic rise in core temperature associated with exercise per se is not the key stimulus responsible for inducing hsp70 mRNA transcription in SkM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12192-011-0291-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227852PMC
January 2012

Regulation of survival gene hsp70.

Cell Stress Chaperones 2012 Jan 28;17(1):1-9. Epub 2011 Aug 28.

School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, ON, Canada.

Rapid expression of the survival gene, inducible heat shock protein 70 (hsp70), is critical for mounting cytoprotection against severe cellular stress, like elevated temperature. Hsp70 protein chaperones the refolding of heat-denatured peptides to minimize proteolytic degradation as a part of an eukaryotically conserved phenomenon referred to as the heat shock response. The physiologic stress associated with exercise, which can include elevated temperature, mechanical damage, hypoxia, lowered pH, and reactive oxygen species generation, may promote protein unfolding, leading to hsp70 gene expression in skeletal myofibers. Although the pre-transcriptional activation of hsp70 gene expression has been thoroughly reviewed, discussion of downstream hsp70 gene regulation is less extensive. The purpose of this brief review was to examine all levels of hsp70 gene regulation in response to heat stress and exercise with a special focus on skeletal myofibers where data are available. In general, while heat stress represses bulk gene expression, hsp70 mRNA expression is enhanced. Post-transcriptionally, intronless hsp70 mRNA circumvents a host of decay pathways, as well as heat stress-repressed pre-mRNA splicing and nuclear export. Pre-translationally, hsp70 mRNA is excluded from stress granules and preferentially translated during heat stress-repressed global cap-dependent translation. Post-translationally, nascent Hsp70 protein is thermodynamically stable at elevated temperatures, allowing for the commencement of chaperoning activity early after synthesis to attenuate the heat shock response and protect against subsequent injury. This review demonstrates that hsp70 mRNA expression is closely coupled with functional protein translation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12192-011-0290-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227850PMC
January 2012

Rapid in vivo whole body composition of rats using cone beam μCT.

J Appl Physiol (1985) 2010 Oct 5;109(4):1162-9. Epub 2010 Aug 5.

Imaging Research Laboratories, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

Precise, noninvasive analysis and quantification of in vivo body composition is essential for research involving longitudinal, small-animal disease models. We investigated the feasibility and precision of a rapid, flat-panel μCT scanner to report whole body adipose tissue volume (ATV), lean tissue volume (LTV), skeletal tissue volume (STV), and bone mineral content (BMC) in 25 postmortem female and 52 live male Sprague-Dawley rats. μCT images, acquired in three 90-mm segments and reconstructed with 308 μm of isotropic voxel spacing, formed contiguous image volumes of each entire rat specimen. Three signal-intensity thresholds (determined to be -186, 5, and 155 HU) were used to classify each voxel as adipose, lean, or skeletal tissue, respectively. Tissue masses from the volume fractions of ATV, LTV, and STV were calculated from assumed tissue densities of 0.95, 1.05, and 1.92 g/cm(-3), respectively. A CT-derived total mass was calculated for each rat and compared with the gravimetrically measured mass, which differed on average for the postmortem female and the live male group by 2.5 and 1.1%, respectively. To evaluate the accuracy of the CT-derived body composition technique, following the live male study excised muscle tissue in the lower right leg of all rats in group B were compared with the image-derived LT measurement of the same regional compartment and found to differ on average by 2.2%. Through repeated CT measurements of postmortem specimens, the whole body ATV, LTV, STV, and BMC measurement analysis gave a precision value of ±0.6, 1.9, 1.7, and 0.5% of the average value, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/japplphysiol.00016.2010DOI Listing
October 2010

Heat shock proteins and exercise: a primer.

Appl Physiol Nutr Metab 2008 Oct;33(5):1050-65

School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, ON N6A3K7, Canada.

Heat shock proteins (HSPs) are, in general, prosurvival molecules within the cellular environment, and the overexpression of even just 1 family of HSPs can lead to protection against and improvements after a variety of stressors. Not surprisingly, a fertile area of study has grown out of efforts to exploit the innate biologic behaviour of HSPs. Exercise, because of the inherent physiologic stresses associated with it, is but 1 stimulus that can result in a robust increase in various HSPs in several tissues, not the least of which happen to be the heart and skeletal muscle. The purpose of this review is to introduce the reader to the major HSP families, the control of their expression, and some of their biologic functions, specifically with respect to the influence of exercise. Moreover, as the first in a series of reviews from a common symposium, we will briefly introduce the concepts presented by the other authors, which include the effects of different exercise paradigms on skeletal muscle HSPs in the adult and aged systems, HSPs as regulators of inflammation, and the ion channel stabilizing effects of HSPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1139/H08-069DOI Listing
October 2008

Is exercise beneficial to the inflammatory bowel diseases? An implication of heat shock proteins.

Med Hypotheses 2009 Jan 1;72(1):84-6. Epub 2008 Oct 1.

School of Kinesiology, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada N6A 3K7.

Inflammatory bowel diseases (IBD) cause the intestines to become inflamed (red and swollen) and typically include Crohn's disease and ulcerative colitis. Heat shock protein (Hsp)70, which exhibits greater expression in the intestines of patients with IBD, may act to protect the intestine against this inflammatory insult. However, most procedures for eliciting this protective response, such as heating and/or pharmacological interventions are non-physiological and can have serious side-effects. Exercise is a biologically relevant means of inducing protective heat shock proteins in the myocardium and other organs but it has yet to be studied in the bowel. We herein hypothesize that (1) exercise will be beneficial in reducing the occurrence of IBD and suppressing intestine inflammatory injuries, (2) exercise will provide protection through induction of anti-inflammatory Hsps. Further studies using both genetically manipulated animal models and animals undergoing exercise are needed to determine the efficacy of exercise and the role of Hsps in inhibiting or treating inflammatory bowel disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mehy.2008.06.045DOI Listing
January 2009

Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise.

Cell Stress Chaperones 2009 Mar 31;14(2):141-50. Epub 2008 Jul 31.

School of Kinesiology, Faculty of Health Sciences, The University of Western Ontario, London, Ontario, Canada.

Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia-reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague-Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia-reperfusion injury. It was observed that administration of the PKC inhibitor chelerythrine chloride (5 mg/kg) suppressed the activation of three exercise-induced PKC isoforms (PKCalpha, PKCdelta, and PKCepsilon) and attenuated the exercise-mediated reduction of myocardial infarct size during ischemia-reperfusion injury. While this study also demonstrated that exercise led to an alteration in the phosphorylation status of Hsp70, this posttranslational modification appeared to be dissociated from PKC activation, as exercise-induced phosphorylation of Hsp70 was unchanged following inhibition of PKC. Taken together, these results indicate that selected isoforms of PKC play an important role in exercise-mediated protection of the myocardium during ischemia-reperfusion injury. However, exercise-induced phosphorylation of Hsp70 does not appear to be a mechanism by which PKC induces this cardioprotective effect.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12192-008-0065-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727986PMC
March 2009

Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-kappaB activation and expression.

Cell Stress Chaperones 2008 Sep 17;13(3):287-96. Epub 2008 Jul 17.

School of Kinesiology, Faculty of Health Sciences, Research Institute, University of Western Ontario, London, Ontario, Canada.

NF-kappaB is a transcription factor implicated in pathological responses that develop during diabetes mellitus, including skeletal muscle atrophy. Given that NF-kappaB activation, protein composition, and content within diabetic skeletal muscle remain generally uncharacterized, a streptozotocin (STZ) model was used to assess NF-kappaB activation, composition, and content. Sprague-Dawley rats were injected with STZ (55 mg/kg) and after 30 days the soleus (SOL), plantaris (PL), red gastrocnemius (RG), and white gastrocnemius (WG) muscles were assessed by electrophoresis mobility shift assay and western blotting. NF-kappaB activation was detected in all muscles examined, but was reduced in RG muscles from diabetic animals. Supershifts indicated NF-kappaB was composed primarily of p50 in diabetic and control animals. The content of both p65 and p52 was elevated in SOL and PL muscles, while p52 was decreased in RG. The coactivating protein, Bcl-3, was increased in WG and RG, but decreased in PL. Both p50 and RelB remained unchanged in all tissues examined. All muscles from diabetic animals demonstrated reduced mass when compared to controls, but only the gastrocnemius demonstrated atrophy as reflected by a reduced muscle-to-body mass ratio. In conclusion, diabetic alterations to the contents and activation of the NF-kappaB protein were tissue-specific, but did not appear to alter dimer composition of constitutively bound NF-kappaB. These results indicate that diabetes may alter NF-kappaB activity and expression in a muscle-specific manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12192-008-0062-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673946PMC
September 2008