Publications by authors named "Aili Guo"

14 Publications

  • Page 1 of 1

The Influence of Bosentan on MicroRNA-27a/PPARγ/ET-1 Signaling Pathway in Pulmonary Artery Hypertension.

Pediatr Cardiol 2021 Apr 15. Epub 2021 Apr 15.

Department of Pediatrics, Qilu Hospital, Cheeloo College of Medicine, Shandong University, No. 107 Wenhuaxi Road, Lixia District, Jinan, 250012, Shandong, China.

Pulmonary artery hypertension (PAH) is a common and serious disease which is characterized by pulmonary vascular remodeling. Bosentan (BST) is the first approved oral targeted drug of endothelin-1 (ET-1) receptor antagonists for the treatment of PAH. MicroRNA-27a (miR-27a) and peroxisome proliferator-activated receptor γ (PPARγ) were found to be related to the pathogenesis of PAH. To further explore the signal transduction mechanism of BST in the treatment of PAH, we examined the effects of BST on endothelin receptors, miR-27a, and PPARγ. Meanwhile, the influence of miR-27a in the formation and development of PAH was discussed. Our results demonstrated that during the pathophysiology of PAH, miR-27a, PPARγ, and ET-1 were cross-inhibited, which indicated that the miR-27a/PPARγ/ET-1 signaling pathway was dysregulated; in addition, BST could competitively bind to ET-1 receptors and inhibit the miR-27a/PPARγ/ET-1 signaling pathway, thereby delaying the proliferation of PASMCs and affecting the development of PAH. Our results give a new understanding of the pathogenesis and treatment of PAH and provide more reliable evidence for the application of BST in the treatment of PAH in the clinic.
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http://dx.doi.org/10.1007/s00246-021-02592-3DOI Listing
April 2021

Natural Compound α-PGG and Its Synthetic Derivative 6Cl-TGQ Alter Insulin Secretion: Evidence for Diminishing Glucose Uptake as a Mechanism.

Diabetes Metab Syndr Obes 2021 24;14:759-772. Epub 2021 Feb 24.

Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of California at Davis (UC Davis) School of Medicine, UC Davis Health Science, Sacramento, CA, 95817, USA.

Purpose: Previously we showed that natural compound α-penta-galloyl-glucose (α-PGG) and its synthetic derivative 6-chloro-6-deoxy-1,2,3,4-tetra-O-galloyl-α-D-glucopyranose (6Cl-TGQ) act to improve insulin signaling in adipocytes by increasing glucose transport. In this study, we investigated the mechanism of actions of α-PGG and 6Cl-TGQ on insulin secretion.

Methods: Mouse islets and/or INS-1832/13 beta-cells were used to test the effects of our compounds on glucose-stimulated insulin secretion (GSIS), intracellular calcium [Ca] using fura-2AM, glucose transport activity via a radioactive glucose uptake assay, intracellular ATP/ADP, and extracellular acidification (ECAR) and mitochondrial oxygen consumption rates (OCAR) using Seahorse metabolic analysis.

Results: Both compounds reduced GSIS in beta-cells without negatively affecting cell viability. The compounds primarily diminished glucose uptake into islets and beta-cells. Despite insulin-like effects in the peripheral tissues, these compounds do not act through the insulin receptor in islets. Further interrogation of the stimulus-secretion pathway showed that all the key metabolic factors involved in GSIS including ECAR, OCAR, ATP/ADP ratios, and [Ca] of INS-1832/13 cells were diminished after the compound treatment.

Conclusion: The compounds suppress glucose uptake of the beta-cells, which consequently slows down the rates of glycolysis and ATP synthesis, leading to decrease in [Ca] and GSIS. The difference between adipocytes and beta-cells in effects on glucose uptake is of great interest. Further structural and functional modifications could produce new compounds with optimized therapeutic potentials for different target cells. The higher potency of synthetic 6Cl-TGQ in enhancing insulin signaling in adipocytes but lower potency in reducing glucose uptake in beta-cells compared to α-PGG suggests the feasibility of such an approach.
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http://dx.doi.org/10.2147/DMSO.S284295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917315PMC
February 2021

Fine Needle Aspiration of Thyroid Nodules Using the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience in a Rural Setting.

Int J Endocrinol 2017 9;2017:9601735. Epub 2017 Feb 9.

Ohio University-Heritage College of Osteopathic Medicine, Athens, OH 45701, USA.

Fine needle aspiration (FNA) remains the first-line diagnostic in management of thyroid nodules and reduces unnecessary surgeries. However, it is still challenging since cytological results are not always straightforward. This study aimed to examine the results of thyroid FNA using the Bethesda system for reporting thyroid cytopathology (TBSRTC) to establish the level of accuracy of FNA procedures in a rural practice setting. A retrospective chart review was conducted on existing thyroid FNA performed in a referral endocrine center between December 2011 and November 2015. A total of 159 patients (18-88 years old) and 236 nodule aspirations were performed and submitted for evaluation. 79% were benign, 3% atypia/follicular lesion of unknown significance (AUS/FLUS), 5% follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 4% suspicious for malignancy (one case was indeed an atypical parathyroid neoplasm by surgical pathology), 2% malignant, and 7% nondiagnostic. Two cases also had advanced molecular analysis on FNA specimens before thyroidectomy. . The diagnostic yield of FNA cytology from our practice in a rural setting suggests that accuracy and specificity are comparable to results from larger centers.
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http://dx.doi.org/10.1155/2017/9601735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5322662PMC
February 2017

B Cell-Activating Factor as a New Potential Marker in Inflammatory Bowel Disease.

Dig Dis Sci 2016 09 7;61(9):2608-18. Epub 2016 Apr 7.

Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.

Background: B cell-activating factor (BAFF) has been proposed to be a regulator of B cell and T cell immune responses and be associated with inflammatory processes in autoimmunity and B cell malignancies. No study has reported the role of BAFF in inflammatory bowel disease (IBD).

Aims: The purpose of this study was to investigate expression and concentrations of BAFF in IBD and determine its value to discriminate patients with IBD.

Methods: Seventy-eight ulcerative colitis (UC) patients, 37 Crohn's disease (CD) patients, 12 irritable bowel syndrome (IBS) patients and 44 healthy controls were recruited. We examined serum and faecal BAFF levels using enzyme-linked immunosorbent assay. Intestinal BAFF expression was analysed in biopsies obtained from IBD patients. Intestinal mucosa localization of BAFF was conducted by immunofluorescence.

Results: The median (25th-75th percentile) serum BAFF concentration (pg/ml) was 1430 (1105-1624) in CD patients, 1472 (1018-1772) in UC patients and 977 (482-1345) in healthy controls. Serum BAFF was 64 % sensitive and 93 % specific for identifying active IBD from healthy controls. The BAFF expression was significantly increased in biopsy specimens from IBD patients. Fecal BAFF concentration was 369 (326-493) pg/ml in CD patients, 542 (358-1758) pg/ml in UC patients, 294 (287-299) pg/ml in IBS patients and 295 (284-309) pg/ml in healthy controls. Fecal BAFF was 90 % sensitive and 96 % specific for identifying active IBD from healthy controls and IBS patients.

Conclusion: The novel association between BAFF and IBD seems to identify that BAFF might regulate the inflammatory process in these diseases and it appears to be a potential marker of IBD.
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http://dx.doi.org/10.1007/s10620-016-4136-zDOI Listing
September 2016

Expression of peptide fragments from proADM and involvement of mitogen-activated protein kinase signaling pathways in pulmonary remodeling induced by high pulmonary blood flow.

Congenit Anom (Kyoto) 2016 Jan;56(1):28-34

Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary arterial remodeling and right ventricular failure. Despite recent advances in pathophysiological mechanism exploration and new therapeutic approaches, PAH remains a challenging condition. In this study, we investigated the roles of the peptide fragments from proadrenomedullin (proADM) such as adrenomedullin (ADM), adrenotensin (ADT), and proadrenomedullin N-terminal 20 peptide (PAMP) during pulmonary remodeling caused by high pulmonary blood flow, and probed the possible involvement of mitogen-activated protein kinase (MAPK) signal transduction pathways. Sixteen rat models of PAH were artificially established by surgically connecting the left common carotid artery to the external jugular vein. We subcutaneously injected an extracellular signal-regulated protein kinase (ERK1/2) inhibitor, PD98059, in eight rats, treated another eight rats with an equal volume of saline. Eight rats without connections served as the control group. We observed that mRNA expression levels of ADM, stress-activated protein kinase (SAPK), and ERK1/2 were significantly elevated in the shunted rats; furthermore, ERK1/2 levels were significantly inhibited by PD98059. Protein levels of ADM, PAMP, p-SAPK, and p-ERK1/2 were significantly higher ADT was lower, and p-p38 remained unchanged in the rat models compared with the controls. However, the protein expression of both ADM and p-ERK1/2 was significantly inhibited by PD98059. Our results suggest that levels of ADM, ADT, and PAMP respond to pulmonary remodeling, and that activation of the SAPK and ERK1/2 signaling pathways is involved in pulmonary hypertension and artery remodeling caused by high pulmonary blood flow.
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http://dx.doi.org/10.1111/cga.12114DOI Listing
January 2016

Autocrine effect of Zn²⁺ on the glucose-stimulated insulin secretion.

Endocrine 2015 Sep 15;50(1):110-22. Epub 2015 Mar 15.

Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, 45701, USA.

It is well known that zinc (Zn(2+)) is required for the process of insulin biosynthesis and the maturation of insulin secretory granules in pancreatic beta (β)-cells, and that changes in Zn(2+) levels in the pancreas have been found to be associated with diabetes. Glucose-stimulation causes a rapid co-secretion of Zn(2+) and insulin with similar kinetics. However, we do not know whether Zn(2+) regulates insulin availability and secretion. Here we investigated the effect of Zn(2+) on glucose-stimulated insulin secretion (GSIS) in isolated mouse pancreatic islets. Whereas Zn(2+) alone (control) had no effect on the basal secretion of insulin, it significantly inhibited GSIS. The application of CaEDTA, by removing the secreted Zn(2+) from the extracellular milieu of the islets, resulted in significantly increased GSIS, suggesting an overall inhibitory role of secreted Zn(2+) on GSIS. The inhibitory action of Zn(2+) was mostly mediated through the activities of KATP/Ca(2+) channels. Furthermore, during brief paired-pulse glucose-stimulated Zn(2+) secretion (GSZS), Zn(2+) secretion following the second pulse was significantly attenuated, probably by the secreted endogenous Zn(2+) after the first pulse. Such an inhibition on Zn(2+) secretion following the second pulse was completely reversed by Zn(2+) chelation, suggesting a negative feedback mechanism, in which the initial glucose-stimulated Zn(2+) release inhibits subsequent Zn(2+) secretion, subsequently inhibiting insulin co-secretion as well. Taken together, these data suggest a negative feedback mechanism on GSZS and GSIS by Zn(2+) secreted from β-cells, and the co-secreted Zn(2+) may act as an autocrine inhibitory modulator.
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http://dx.doi.org/10.1007/s12020-015-0568-zDOI Listing
September 2015

Diet is critical for prolonged glycemic control after short-term insulin treatment in high-fat diet-induced type 2 diabetic male mice.

PLoS One 2015 29;10(1):e0117556. Epub 2015 Jan 29.

Ohio University Heritage College of Osteopathic Medicine, Athens, Ohio 45701, United States of America; The Diabetes Institute at Ohio University, Athens, Ohio 45701, United States of America.

Background: Clinical studies suggest that short-term insulin treatment in new-onset type 2 diabetes (T2DM) can promote prolonged glycemic control. The purpose of this study was to establish an animal model to examine such a "legacy" effect of early insulin therapy (EIT) in long-term glycemic control in new-onset T2DM. The objective of the study was to investigate the role of diet following onset of diabetes in the favorable outcomes of EIT.

Methodology: As such, C57BL6/J male mice were fed a high-fat diet (HFD) for 21 weeks to induce diabetes and then received 4 weeks of daily insulin glargine or sham subcutaneous injections. Subsequently, mice were either kept on the HFD or switched to a low-fat diet (LFD) for 4 additional weeks.

Principal Findings: Mice fed a HFD gained significant fat mass and displayed increased leptin levels, increasing insulin resistance (poor HOMA-IR) and worse glucose tolerance test (GTT) performance in comparison to mice fed a LFD, as expected. Insulin-treated diabetic mice but maintained on the HFD demonstrated even greater weight gain and insulin resistance compared to sham-treated mice. However, insulin-treated mice switched to the LFD exhibited a better HOMA-IR compared to those mice left on a HFD. Further, between the insulin-treated and sham control mice, in spite of similar HOMA-IR values, the insulin-treated mice switched to a LFD following insulin therapy did demonstrate significantly better HOMA-B% values than sham control and insulin-treated HFD mice.

Conclusion/interpretation: Early insulin treatment in HFD-induced T2DM in C57BL6/J mice was only beneficial in animals that were switched to a LFD after insulin treatment which may explain why a similar legacy effect in humans is achieved clinically in only a portion of cases studied, emphasizing a vital role for diet adherence in diabetes control.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117556PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4310595PMC
February 2016

Enhanced cardiac Akt/protein kinase B signaling contributes to pathological cardiac hypertrophy in part by impairing mitochondrial function via transcriptional repression of mitochondrion-targeted nuclear genes.

Mol Cell Biol 2015 Mar 22;35(5):831-46. Epub 2014 Dec 22.

Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, Utah, USA Fraternal Order of Eagles Diabetes Research Center and Division of Endocrinology and Metabolism, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA

Sustained Akt activation induces cardiac hypertrophy (LVH), which may lead to heart failure. This study tested the hypothesis that Akt activation contributes to mitochondrial dysfunction in pathological LVH. Akt activation induced LVH and progressive repression of mitochondrial fatty acid oxidation (FAO) pathways. Preventing LVH by inhibiting mTOR failed to prevent the decline in mitochondrial function, but glucose utilization was maintained. Akt activation represses expression of mitochondrial regulatory, FAO, and oxidative phosphorylation genes in vivo that correlate with the duration of Akt activation in part by reducing FOXO-mediated transcriptional activation of mitochondrion-targeted nuclear genes in concert with reduced signaling via peroxisome proliferator-activated receptor α (PPARα)/PGC-1α and other transcriptional regulators. In cultured myocytes, Akt activation disrupted mitochondrial bioenergetics, which could be partially reversed by maintaining nuclear FOXO but not by increasing PGC-1α. Thus, although short-term Akt activation may be cardioprotective during ischemia by reducing mitochondrial metabolism and increasing glycolysis, long-term Akt activation in the adult heart contributes to pathological LVH in part by reducing mitochondrial oxidative capacity.
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http://dx.doi.org/10.1128/MCB.01109-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323486PMC
March 2015

Role of the extracellular signal-regulated kinase 1/2 signaling pathway in the process of thrombin-promoting airway remodeling in ovalbumin-allergic rats.

Immunopharmacol Immunotoxicol 2015 Feb;37(1):26-34

Department of Pediatrics .

Context: Although it is recognized that thrombin plays a key role in airway remodeling during chronic asthma. In a previous study, we have proved that thrombin promotes airway remodeling via PAR-1 in OVA-allergic rats, but little is known about intracellular signaling pathway involved in the event.

Objective: In this study, we intend to explore the impact of pERK1/2 signaling pathway on the process of thrombin-induced airway remodeling in OVA-allergic rats.

Materials And Methods: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06, and pERK1/2 inhibitor PD98059 varied for different groups. The expression of pERK1/2 was analyzed by western blot and RT-PCR. Secretion of TGF-β1 and IL-6 was detected by ELISA.

Results: The expression of pERK1/2 was higher in the airway of asthmatic rats than those of normal rats, and was significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was enhanced by thrombin but weakened by pERK1/2 inhibitor. Expression of growth factors and IL-6 in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and pERK1/2 inhibitor treatment.

Conclusion: These results suggest that ERK1/2 signaling pathway may play an important role in the process of thrombin-promoting airway remodeling in OVA-allergic rats, and pERK1/2 inhibitor effectively inhibits the process.
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http://dx.doi.org/10.3109/08923973.2014.993083DOI Listing
February 2015

Thrombin promotes airway remodeling via protease-activated receptor-1 and transforming growth factor-β1 in ovalbumin-allergic rats.

Inhal Toxicol 2013 Aug;25(10):577-86

Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong Univeristy, Jinan, China.

Background: Protease-activated receptor-1 (PAR-1) is widely distributed in platelets and involved in coagulation cascade activated by thrombin. In this study, we intend to explore the role of PAR-1 in the process of thrombin-inducing transforming growth factor-β1 (TGF-β1) to promote airway remodeling in ovalbumin (OVA)-allergic rats.

Materials And Methods: A rat model of chronic asthma was set up by systemic sensitization and repeated challenge to OVA. The doses of thrombin, recombinant hirudin, PAR-1 inhibitor ER-112780-06 varied for different groups. We evaluated the bronchoalveolar lavage fluid (BALF) concentration of thrombin in these groups. The protein and gene expression of PAR-1 was assessed and the expression of TGF-β1 was also detected.

Results: The PAR-1 mRNA level and the protein level were higher in the airway of asthmatic rats than those of normal rats, and were significantly increased by thrombin treatment but decreased by thrombin-inhibitor treatment. Airway remodeling was strengthened by thrombin but weakened by thrombin inhibitor and PAR-1 antagonist. Expression of TGF-β1 protein in asthmatic rats was significantly increased by thrombin treatment and decreased by thrombin-inhibitor treatment and PAR-1 antagonist treatment.

Conclusion: The expression of PAR-1 is regulated by thrombin that induces the expression of TGF-β1 to promote airway remodeling via PAR-1 in OVA-allergic rats.
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http://dx.doi.org/10.3109/08958378.2013.813995DOI Listing
August 2013

The effect of recombinant stromal cell-derived factor-1 treatment on hypoxic-ischemic brain injury in neonatal mice.

Neuropediatrics 2012 Dec 8;43(6):320-31. Epub 2012 Oct 8.

Department of Pediatrics, Jinan Central Hospital affiliated to Shandong University, Jinan, China.

Background: Stromal cell-derived factor-1 (SDF-1) plays a critical role in adult brain injury repair including neurogenesis and vasculogenesis. However, the effects of recombinant SDF-1(rSDF-1) treatment on hypoxic-ischemic (HI) brain injury in neonatal mice are not clear.

Materials And Methods: Seven-day-old (P7) C57BL/6J mice were divided into sham group, control group, and rSDF-1 group. Mice brains were collected to determine histopathological damage and the expression level of SDF-1, caspase-3, and Ki67 on P8, P10, P14, and P21. Passive avoidance and elevated plus-maze tests were also assessed on P20 and P21.

Results: Compared with control group, rSDF-1 treatment increased the weight ratio of left and right brain hemisphere (p < 0.05), reduced the number of electric foot shocks (p < 0.05) and the percentage of time spent in the open arms (p < 0.05), meanwhile, increased the retention latency (p < 0.05) and the percentage of time spent in the enclosed arms (p < 0.05) on P20 and P21. High expression of Ki67 and low expression of caspase-3 were also observed.

Discussion: This study showed that rSDF-1 treatment effectively alleviated brain injury shown by reducing in caspase-3 expression and increasing in Ki67 expression. Moreover, rSDF-1 treatment significantly improved behavioral performances in juvenile mice after HI.
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http://dx.doi.org/10.1055/s-0032-1325121DOI Listing
December 2012

Analysis of use of an automated bolus calculator reduces fear of hypoglycemia and improves confidence in dosage accuracy in type 1 diabetes mellitus patients treated with multiple daily insulin injections.

J Diabetes Sci Technol 2012 Jan 1;6(1):150-2. Epub 2012 Jan 1.

Appalachian Rural Health Institute Diabetes/Endocrine Center at The Heritage College of Osteopathic Medicine, Ohio University, Athens, Ohio, USA.

In this issue of Journal of Diabetes Science and Technology, Barnard and colleagues evaluate the use of the ACCU-CHEK® Aviva Expert blood glucose meter/bolus advisor system in patients with type 1 diabetes mellitus. Hypoglycemia is a major limiting factor to intensive glucose control, and fear of hypoglycemia, especially in those who have experienced severe reactions, is a major barrier. The bolus advisor improved overall glucose control and increased adherence by overcoming the patients' fear of hypoglycemia, giving them more confidence to give adequate doses of insulin to control hyperglycemia. In this review, we discuss other human factors that become barriers to intensive control, which can benefit from new technologies, including numeracy literacy, information overload, time required for diabetes self-care, and device incompatibility.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320832PMC
http://dx.doi.org/10.1177/193229681200600118DOI Listing
January 2012

Saxagliptin: A Selective DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus.

Clin Med Insights Endocrinol Diabetes 2011 12;4:1-12. Epub 2011 Jan 12.

Department of Family Medicine,OU-COM, 349 Grosvenor Hall, Athens OH 45701, Ohio University College of Osteopathic Medicine (OU-COM), Athens OH 45701.

The prevalence of type 2 diabetes mellitus is high and growing rapidly. Suboptimal glycemic control provides opportunities for new treatment options to improve the morbidity and mortality of this progressive disease. Saxagliptin, a selective DPP-4 inhibitor, increases endogenous incretin levels and incretin acitivty. In controlled clinical trials saxagliptin reduces both fasting and postprandial glucose and works in monotherapy and in combination with metformin, TZDs and sulfonylureas. Saxagliptin has a very favourable side effect profile and may have other beneficial non-glycemic effects. The authors review the current available evidence for the safety, efficacy and saxagliptin's place in therapy for type 2 diabetes mellitus. As understanding of the incretin hormones (GLP-1, GIP) expand we may see additional important non-glycemic effects that may affect the chronic management of type 2 diabetes mellitus.
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http://dx.doi.org/10.4137/CMED.S5114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3411543PMC
August 2012

A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy.

Cell Metab 2007 Oct;6(4):294-306

Program in Human Molecular Biology and Genetics and Division of Endocrinology, Metabolism, and Diabetes, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.

Physiological cardiac hypertrophy is associated with mitochondrial adaptations that are characterized by activation of PGC-1alpha and increased fatty acid oxidative (FAO) capacity. It is widely accepted that phosphatidylinositol 3-kinase (PI3K) signaling to Akt1 is required for physiological cardiac growth. However, the signaling pathways that coordinate physiological hypertrophy and metabolic remodeling are incompletely understood. We show here that activation of PI3K is sufficient to increase myocardial FAO capacity and that inhibition of PI3K signaling prevents mitochondrial adaptations in response to physiological hypertrophic stimuli despite increased expression of PGC-1alpha. We also show that activation of the downstream kinase Akt is not required for the mitochondrial adaptations that are secondary to PI3K activation. Thus, in physiological cardiac growth, PI3K is an integrator of cellular growth and metabolic remodeling. Although PI3K signaling to Akt1 is required for cellular growth, Akt-independent pathways mediate the accompanying mitochondrial adaptations.
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http://dx.doi.org/10.1016/j.cmet.2007.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2084219PMC
October 2007