5,672 results match your criteria American journal of physiology. Endocrinology and metabolism[Journal]


Reply to Jakovac: About COVID-19 and vitamin D.

Am J Physiol Endocrinol Metab 2020 06;318(6):E838

Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.

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http://dx.doi.org/10.1152/ajpendo.00185.2020DOI Listing

CTRP12 ablation differentially affects energy expenditure, body weight, and insulin sensitivity in male and female mice.

Am J Physiol Endocrinol Metab 2020 May 18. Epub 2020 May 18.

Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Center for Metabolism and Obesity Research, Johns Hopkins University School of Medicine, Baltimore, Maryland.

Secreted hormones facilitate tissue crosstalk to maintain energy balance. We have previously described C1q/TNF-related protein 12 (CTRP12) as a novel metabolic hormone. Gain-of-function and partial deficiency mouse models have highlighted important roles for this fat-derived adipokine in modulating systemic metabolism. Read More

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http://dx.doi.org/10.1152/ajpendo.00533.2019DOI Listing

Glucagon-Dependent Suppression of mTORC1 is Associated with Upregulation of Hepatic FGF21 mRNA Translation.

Am J Physiol Endocrinol Metab 2020 May 18. Epub 2020 May 18.

Department of Cellular and Molecular Physiology, Penn State College of Medicine, 500 University Drive, Hershey PA 17033, United States.

Fibroblast growth factor 21 (FGF21) is a peptide hormone that acts to enhance insulin sensitivity and reverse many of the metabolic defects associated with consumption of a high-fat diet. Recent studies show that the liver is the primary source of FGF21 in the blood, and that hepatic FGF21 expression is upregulated by glucagon. Interestingly, glucagon acts to upregulate FGF21 production by primary cultures of rat hepatocytes and H4IIE and HepG2 hepatocarcinoma cells independent of changes in FGF21 mRNA abundance, suggesting that FGF21 protein expression is regulated post-transcriptionally. Read More

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http://dx.doi.org/10.1152/ajpendo.00555.2019DOI Listing

Statins activate the NLRP3 inflammasome and impair insulin signalling via p38 and mTOR.

Am J Physiol Endocrinol Metab 2020 May 18. Epub 2020 May 18.

Department of Biochemistry and Biomedical Sciences and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton ON, L8N 3Z5 Canada; Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5.

Statins lower cholesterol and risk of cardiovascular disease. Statins can increase blood glucose and risk of new onset diabetes. It is unclear why statins can have opposing effects on lipids versus glucose. Read More

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http://dx.doi.org/10.1152/ajpendo.00125.2020DOI Listing

Is there an impact of the COVID-19 pandemic on male fertility? The ACE2 connection.

Am J Physiol Endocrinol Metab 2020 May 18. Epub 2020 May 18.

Azrieili Faculty of Medicine in Galilee, Safed, Bar-Ilan University, Israel.

The viral pandemic of the coronavirus disease 2019 (COVID-19), generated by a novel mutated severe acute respiratory syndrome coronavirus (SARS-CoV-2), is turning into a serious worldwide public health emergency, evolving exponentially. While the main organ targeted in this diseased are the lungs, other vital organs such as the heart and kidney may be implicated. The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). Read More

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http://dx.doi.org/10.1152/ajpendo.00183.2020DOI Listing

Glycemic control of type 2 diabetic patients with coronavirus disease during hospitalization: a proposal for early insulin therapy.

Am J Physiol Endocrinol Metab 2020 Jun;318(6):E835-E837

Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel.

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http://dx.doi.org/10.1152/ajpendo.00163.2020DOI Listing

Lower Oxygen Consumption and Complex I Activity in Mitochondria Isolated from Skeletal Muscle of Fetal Sheep with Intrauterine Growth Restriction.

Am J Physiol Endocrinol Metab 2020 May 12. Epub 2020 May 12.

Physiological Sciences Graduate Interdisciplinary Program, University of Arizona, Tucson, Arizona; School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona, United States.

Fetal sheep with placental insufficiency-induced intrauterine growth restriction (IUGR) have lower hind-limb oxygen consumption rates (OCR), indicating depressed mitochondrial oxidative phosphorylation capacity in their skeletal muscle. We hypothesized that OCRs are lower in skeletal muscle mitochondria from IUGR fetuses due to reduced electron transport chain (ETC) activity and lower abundances of Tricarboxylic Acid (TCA) cycle enzymes. IUGR sheep fetuses (n=12) were created with mid-gestation maternal hyperthermia and compared to control fetuses (n=12). Read More

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http://dx.doi.org/10.1152/ajpendo.00057.2020DOI Listing

Covid-19 associated SIADH; a clue in the times of pandemic!

Am J Physiol Endocrinol Metab 2020 May 12. Epub 2020 May 12.

Medicine Department, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.

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http://dx.doi.org/10.1152/ajpendo.00178.2020DOI Listing

Erythropoietin-producing hepatocellular A7 restrains estrogen-negative feedback of luteinizing hormone via ephrin A5 in the hypothalamus of female rats.

Am J Physiol Endocrinol Metab 2020 May 12. Epub 2020 May 12.

Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.

We have previously shown that systemic injection of exogenous erythropoietin-producing hepatocellular (EPH) A7-Fc raises serum luteinizing hormone (LH) levels before ovulation in female rats, indicating the induction of EPHA7 in ovulation. In this study, we aimed to identify the mechanism and hypothalamus-pituitary-ovary (HPO) axis level underlying the promotion of LH secretion by EPHA7. Using an ovariectomized (OVX) rat model, in conjunction with low-dose estradiol (E) treatment, we investigated the association between EPHA7-ephrin (EFN) A5 signaling and E-negative feedback. Read More

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http://dx.doi.org/10.1152/ajpendo.00046.2020DOI Listing

ß-Hydroxybutyrate is Reduced in Humans with Obesity-Related NAFLD and Displays a Dose-Dependent Effect on Skeletal Muscle Mitochondrial Respiration In Vitro.

Am J Physiol Endocrinol Metab 2020 May 12. Epub 2020 May 12.

Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA; Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland OH; Metabolic Translational Research Center, Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and skeletal muscle insulin resistance. Reduced hepatic ketogenesis may promote these pathologies, but data are inconclusive in humans and the link between NAFLD and exacerbated skeletal muscle insulin resistance remains obscure. Objective We investigated individuals with obesity-related NAFLD and hypothesized that ß-hydroxybutyrate (ßOHB; the predominant ketone species) would be reduced and related to hepatic fat accumulation and skeletal muscle insulin resistance. Read More

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http://dx.doi.org/10.1152/ajpendo.00058.2020DOI Listing

Reducing 14-3-3ζ expression influences adipocyte maturity and impairs function.

Am J Physiol Endocrinol Metab 2020 May 5. Epub 2020 May 5.

Department of Medicine, Université of Montréal, Montréal, QC, Canada; Cardiometabolic axis, Centre de recherche de Centre hospitalier de l'Université de Montréal, Montréal, QC, Canada.

One of the primary metabolic functions of a mature adipocyte is to supply energy via lipolysis, or the catabolism of stored lipids. Adipose triacylglycerol lipase (ATGL) and hormone-sensitive lipase (HSL) are critical lipolytic enzymes, and their phosphorylation generates phospho-binding sites for 14-3-3 proteins, a ubiquitously expressed family of molecular scaffolds. While we previously identified essential roles of the 14-3-3ζ isoform in murine adipogenesis, the presence of 14-3-3 protein binding sites on ATGL and HSL suggests that 14-3-3zcould also influence mature adipocyte processes like lipolysis. Read More

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http://dx.doi.org/10.1152/ajpendo.00093.2020DOI Listing

Regulation of the Ca channel αδ-1 subunit expression by epidermal growth factor via the ERK/ELK-1 signaling pathway.

Am J Physiol Endocrinol Metab 2020 May 5. Epub 2020 May 5.

Department of Cell Biology, Centre for Research and Advanced Studies (Cinvestav), Mexico City, Mexico.

Voltage-gated Ca (Ca) channels are expressed in endocrine cells where they contribute to hormone secretion. Diverse chemical messengers including epidermal growth factor (EGF) are known to affect the expression of Ca channels. Previous studies have shown that EGF increases Ca currents in GH3 pituitary cells by increasing the number of high voltage-activated (HVA) Ca channels at the cell membrane, which results in enhanced prolactin (PRL) secretion. Read More

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http://dx.doi.org/10.1152/ajpendo.00007.2020DOI Listing

Relative lipid oxidation associates directly with mitochondrial fusion phenotype and mitochondria-sarcoplasmic reticulum interactions in human skeletal muscle.

Am J Physiol Endocrinol Metab 2020 Jun 5;318(6):E848-E855. Epub 2020 May 5.

Escuela de Kinesiología, Facultad de Medicina, Universidad Finis Terrae, Santiago, Chile.

Disturbances in skeletal muscle lipid oxidation might induce ectopic fat deposition and lipotoxicity. Nevertheless, the cellular mechanisms that regulate skeletal muscle lipid oxidation have not been fully determined. We aimed to determine whether there was an association between relative whole body lipid oxidation and mitochondrial size or mitochondria-sarcoplasmic reticulum interactions in the skeletal muscle. Read More

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http://dx.doi.org/10.1152/ajpendo.00025.2020DOI Listing

Identification of scavenger receptor BI as potential screening candidate for congenital primary adrenal insufficiency in humans.

Authors:
Menno Hoekstra

Am J Physiol Endocrinol Metab 2020 May 5. Epub 2020 May 5.

Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Gorlaeus Laboratories, Einsteinweg 55, 2333CC Leiden, Netherlands.

Glucocorticoids belong to the superfamily of steroid hormones that are synthesized from the common precursor cholesterol. Adrenal-derived glucocorticoids, e.g. Read More

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http://dx.doi.org/10.1152/ajpendo.00069.2020DOI Listing

Impacts of rat hind-limb Fndc5/Irisin overexpression upon muscle and adipose tissue metabolism.

Am J Physiol Endocrinol Metab 2020 May 5. Epub 2020 May 5.

MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and Nottingham NIHR BRC, School of Medicine, University of Nottingham, Derby, United Kingdom.

Objective: Myokines, such as Irisin, have been purported to exert physiological effects on skeletal muscle in an autocrine/paracrine fashion. In this study, we aimed to investigate the mechanistic role of in vivo Fndc5/Irisin upregulation in muscle.

Methods: Overexpression (OE) of Fndc5 in rat hind-limb muscle was achieved by in vivo electro-transfer i. Read More

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http://dx.doi.org/10.1152/ajpendo.00034.2020DOI Listing

Dynamic Glucose Disposal is Driven by Reduced Endogenous Glucose Production in Response to Voluntary Wheel Running: A Stable Isotope Approach.

Am J Physiol Endocrinol Metab 2020 Apr 28. Epub 2020 Apr 28.

Pennington Biomedical Research Center, Baton Rouge LA, United States.

To resolve both the systems level and molecular mechanisms responsible for exercise induced improvements in glucose tolerance, we sought to test the effect of voluntary wheel running exercise on postprandial glucose dynamics. We utilized a stable isotope labeled oral glucose tolerance test (SI-OGTT) incorporating complimentary deuterium glucose tracers at 1:1 ratio (2-H-glucose and 6-6 H-glucose; 2g/kg lean body mass) to distinguish between endogenous glucose production (EGP) and whole-body glucose disposal. SI-OGTT was performed in C57BL/6J mice after 8 weeks on a high fat diet (45% fat). Read More

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http://dx.doi.org/10.1152/ajpendo.00450.2019DOI Listing

Melatonin ameliorates excessive PINK1/Parkin-mediated mitophagy by enhancing SIRT1 expression in granulosa cells of PCOS.

Am J Physiol Endocrinol Metab 2020 Apr 28. Epub 2020 Apr 28.

Reproductive Medicine Center, Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, 210008, China.

Mitochondrial injury in granulosa cells is associated with the pathogenesis of polycystic ovary syndrome (PCOS). However, the protective effects of melatonin against mitochondrial injury in the granulosa cells of PCOS remain unclear. In this study, decreased mitochondrial membrane potential and mtDNA content, increased number of autophagosomes were found in the granulosa cells of PCOS patients and the DHT-treated KGN cells, with decreased protein level of the autophagy substrate P62 and increased levels of the cellular autophagy markers Beclin-1 and LC3B-II, while the protein levels of PINK1 and Parkin were increased and the level of SIRT1 was decreased. Read More

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http://dx.doi.org/10.1152/ajpendo.00006.2020DOI Listing

Decrease in SHP-1 Enhances Myometrium Remodeling via FAK Activation Leading to Labor.

Am J Physiol Endocrinol Metab 2020 Apr 28. Epub 2020 Apr 28.

Department of Physiology, Second Military Medical University, Shanghai 200433, China; The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

Preterm birth is one of the most common complications during human pregnancy, and associated with a dramatic switch within the uterus from quiescence to contractility. However, the mechanisms underlying uterine remodeling are largely unknown. Protein kinases and phosphatases play critical roles in regulating the phosphorylation of proteins involved in the smooth muscle cell functions. Read More

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http://dx.doi.org/10.1152/ajpendo.00068.2020DOI Listing

Chlamydia muridarum infection differentially alters smooth muscle function in mouse uterine horn and cervix.

Am J Physiol Endocrinol Metab 2020 Apr 21. Epub 2020 Apr 21.

School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW.

Chlamydia trachomatis infection is a primary cause of reproductive tract diseases including infertility. Previous studies showed that this infection alters physiological activities in mouse oviducts. Whether this occurs in the uterus and cervix has never been investigated. Read More

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http://dx.doi.org/10.1152/ajpendo.00513.2019DOI Listing

Role of enhanced glucocorticoid receptor sensitivity in inflammation in PTSD: Insights from computational model for circadian-neuroendocrine-immune interactions.

Am J Physiol Endocrinol Metab 2020 Apr 21. Epub 2020 Apr 21.

Harvard John Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States.

Although glucocorticoid resistance contributes to increased inflammation, individuals with post-traumatic stress disorder (PTSD) exhibit increased glucocorticoid receptor (GR) sensitivity along with increased inflammation. It is not clear how inflammation co-exists with a hyper-responsive hypothalamic pituitary adrenal axis (HPA axis). To understand this better, we developed and analyzed an integrated mathematical model for the HPA axis and the immune system. Read More

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http://dx.doi.org/10.1152/ajpendo.00398.2019DOI Listing

Long-term hypercortisolism induces lipogenesis promoting palmitic acid accumulation and inflammation in visceral adipose tissue compared to HFD-induced obesity.

Am J Physiol Endocrinol Metab 2020 Apr 21. Epub 2020 Apr 21.

Group of Endocrine Disorders, IDIBAPS, Barcelona, Spain;. Endocrinology and Nutrition Service, Hospital Clinic, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Medicine, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona.

Glucocorticoids (GCs) play critical roles in adipose tissue metabolism. Here, we compare in a mouse model the effects of chronic glucocorticoid excess and diet-induced obesity in the white adipose tissue mass and distribution, by focusing on the visceral adipose tissue fatty acid composition changes, the role of de novo lipogenesis (DNL) and the inflammatory state. We used a non-invasive mouse model of hypercortisolism to compare GCs-induced effects on adipose tissue with diet-induced obesity (HFD 45%) and control mice after ten weeks of treatment. Read More

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http://dx.doi.org/10.1152/ajpendo.00516.2019DOI Listing

RANKL induces beige adipocyte differentiation in preadipocytes.

Am J Physiol Endocrinol Metab 2020 Jun 21;318(6):E866-E877. Epub 2020 Apr 21.

Laboratory of Cell and Tissue Biology, Department of Cell and Molecular Biology and Pathogenic Bioagents, Ribeirao Preto Medical School, University of São Paulo, Ribeirao Preto, São Paulo, Brazil.

The receptor activator of nuclear factor-κB (NF-κB) (RANK), its ligand (RANKL), and the decoy receptor osteoprotegerin (OPG) are a triad of proteins that regulate bone metabolism, and serum OPG is considered a biomarker for cardiovascular diseases and Type 2 diabetes; however, the implications of OPG in adipose tissue metabolism remains elusive. In this study, we investigate RANK-RANKL-OPG signaling in white adipose tissue browning. Histological analysis of osteoprotegerin knockout (OPG-/-) mice showed subcutaneous white adipose tissue (sWAT) browning, resistance for high-fat diet-induced weight gain, and preserved glucose metabolism compared with wild-type (WT) mice. Read More

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http://dx.doi.org/10.1152/ajpendo.00397.2019DOI Listing
June 2020
3.785 Impact Factor

Dietary carbohydrates modulate metabolic and β-cell adaptation to high-fat diet-induced obesity.

Am J Physiol Endocrinol Metab 2020 Jun 21;318(6):E856-E865. Epub 2020 Apr 21.

Department of Physiology and Biomedical Engineering, Mayo Clinic School of Medicine, Rochester, Minnesota.

Obesity is associated with several chronic comorbidities, one of which is type 2 diabetes mellitus (T2DM). The pathogenesis of obesity and T2DM is influenced by alterations in diet macronutrient composition, which regulate energy expenditure, metabolic function, glucose homeostasis, and pancreatic islet cell biology. Recent studies suggest that increased intake of dietary carbohydrates plays a previously underappreciated role in the promotion of obesity and consequent metabolic dysfunction. Read More

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http://dx.doi.org/10.1152/ajpendo.00539.2019DOI Listing

Biological plausibility for interactions between dietary fat, resveratrol, , and SARS-CoV illness severity.

Am J Physiol Endocrinol Metab 2020 05 20;318(5):E830-E833. Epub 2020 Apr 20.

Centre Nutrition, Santé et Société (NUTRISS)-Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Quebec City, Quebec, Canada.

The angiotensin converting enzyme-2 (ACE2) cellular receptor is responsible for the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), thus impacting the entrance and clearance of the virus. Studies demonstrate that upregulation of has a protective effect on SARS-CoV-2 illness severity. Moreover, animal studies demonstrate that dietary intake can modulate gene expression and function. Read More

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http://dx.doi.org/10.1152/ajpendo.00150.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215091PMC

Can spironolactone be used to prevent COVID-19-induced acute respiratory distress syndrome in patients with hypertension?

Am J Physiol Endocrinol Metab 2020 05;318(5):E587-E588

Adrenal and Hypertension Unit, Endocrinology, Department of Medicine, Federal University of São Paulo, São Paulo, Brazil.

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http://dx.doi.org/10.1152/ajpendo.00136.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191632PMC

COVID-19 and vitamin D-Is there a link and an opportunity for intervention?

Authors:
Hrvoje Jakovac

Am J Physiol Endocrinol Metab 2020 05;318(5):E589

Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.

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http://dx.doi.org/10.1152/ajpendo.00138.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191631PMC

HDL-apoA-I kinetics in response to 16 wk of exercise training in men with nonalcoholic fatty liver disease.

Am J Physiol Endocrinol Metab 2020 Jun 14;318(6):E839-E847. Epub 2020 Apr 14.

Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.

Nonalcoholic fatty liver disease (NAFLD) is characterized by low-circulating concentration of high-density lipoprotein cholesterol (HDL-C) and raised triacylglycerol (TAG). Exercise reduces hepatic fat content, improves insulin resistance and increases clearance of very-low-density lipoprotein-1 (VLDL). However, the effect of exercise on TAG and HDL-C metabolism is unknown. Read More

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http://dx.doi.org/10.1152/ajpendo.00019.2020DOI Listing
June 2020
3.785 Impact Factor

High-glucose mixed nutrient meal ingestion impairs skeletal muscle microvascular blood flow in healthy young males.

Am J Physiol Endocrinol Metab 2020 Apr 14. Epub 2020 Apr 14.

Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Geelong, Australia.

Background And Aims: Oral glucose ingestion leads to impaired muscle microvascular blood flow (MBF) which likely contributes to acute hyperglycemia-induced insulin resistance. We investigated whether incorporating lipids and protein into a high-glucose load could prevent postprandial MBF dysfunction.

Methods: Ten healthy young males (age: mean 27 years old, 95% lower and upper confidence interval [24, 30]; height: 180 cm [174, 185]; weight: 77 kg [70, 84]) ingested a high-glucose (1. Read More

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http://dx.doi.org/10.1152/ajpendo.00540.2019DOI Listing

GABAergic input through GABAB receptors is necessary during a perinatal window to shape gene expression of factors critical to reproduction such as Kiss1.

Am J Physiol Endocrinol Metab 2020 Apr 14. Epub 2020 Apr 14.

Laboratorio de Neuroendocrinología, Instituto de Biología y Medicina Experimental (IBYME11 CONICET), Buenos Aires.

Lack of GABAB receptors in GABAB1KO mice decreases neonatal ARC Kiss1 expression in females that show impaired reproduction as adults. Here our aim was to selectively impair GABAB signaling during a short postnatal period to evaluate its impact on the reproductive system. Neonatal male and female mice were injected with GABAB antagonist CGP55845 (1 mg/kg BW, sc, CGP) or saline from postnatal day 2 (PND2)-PND6, three times/day (8AM, 1PM, 6PM). Read More

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http://dx.doi.org/10.1152/ajpendo.00547.2019DOI Listing

Comparative label-free mass spectrometric analysis of temporal changes in the skeletal muscle proteome after impact trauma in rats.

Am J Physiol Endocrinol Metab 2020 Apr 7. Epub 2020 Apr 7.

School of Biomedical Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.

Proteomics offers the opportunity to identify and quantify many proteins, and to explore how they correlate and interact with each other in biological networks. This study aimed to characterize changes in the muscle proteome during the destruction, repair and early remodeling phases after impact trauma in male Wistar rats. Muscle tissue was collected from uninjured control rats and rats that were euthanized between 6 h to 14 d after impact injury. Read More

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http://dx.doi.org/10.1152/ajpendo.00433.2019DOI Listing

The inducible β5i proteasome subunit contributes to proinsulin degradation in GRP94 deficient β cells and is overexpressed in type 2 diabetes pancreatic islets.

Am J Physiol Endocrinol Metab 2020 Apr 7. Epub 2020 Apr 7.

Laboratory of Immuno-endocrinology, Inflammation, Metabolism and Oxidation Section, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Proinsulin is a misfolding-prone protein and its efficient breakdown is critical, when b-cells are confronted with high insulin biosynthetic demands, to prevent endoplasmic reticulum stress, a key trigger of secretory dysfunction and, if uncompensated, apoptosis. Proinsulin degradation is thought to be performed by the constitutively expressed standard proteasome, while the roles of other proteasomes are unknown. We recently demonstrated that deficiency of the proinsulin chaperone GRP94 causes impaired proinsulin-handling and defective insulin-secretion associated with a compensated endoplasmic reticulum stress-response. Read More

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http://dx.doi.org/10.1152/ajpendo.00372.2019DOI Listing

Utilization of biomarkers as predictors of skeletal muscle mitochondrial content after physiological intervention and in clinical settings.

Am J Physiol Endocrinol Metab 2020 Apr 7. Epub 2020 Apr 7.

Department of Public Health, Aarhus University, Aarhus, Denmark.

The measurement of mitochondrial content is essential for bioenergetic research as it provides a tool to evaluate if changes in mitochondrial function are strictly due to changes in content or other mechanisms that influence function. In this perspective, we argue that commonly used biomarkers of mitochondrial content may possess limited utility for capturing changes in content with physiological intervention. Moreover, we argue that they may not provide reliable estimates of content in certain pathological situations. Read More

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http://dx.doi.org/10.1152/ajpendo.00101.2020DOI Listing

Alanine, arginine, cysteine, and proline but not glutamine are substrates for and acute mediators of the liver-alpha cell axis in female mice.

Am J Physiol Endocrinol Metab 2020 Apr 7. Epub 2020 Apr 7.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation (NNF) Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen.

Aim: To identify the amino acids that stimulate glucagon secretion in mice and whose metabolism depends on glucagon receptor signaling.

Methods: Pancreata of female C57BL/6JRj mice were perfused with 19 individual amino acids and pyruvate (at 10 mM) and secretion of glucagon was assessed using a specific glucagon radioimmunoassay. Separately, a glucagon receptor antagonist (GRA; 25-2648, 100 mg/kg) or vehicle was administered to female C57BL/6JRj mice three hours prior to an intraperitoneal injection of four different isomolar amino acid mixtures (in total 7 µmol/g body weight); mixture 1: alanine, arginine, cysteine, and proline; mixture 2: aspartate, glutamate, histidine, and lysine; mixture 3: citrulline, methionine, serine, and threonine; and mixture 4: glutamine, leucine, isoleucine, and valine. Read More

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http://dx.doi.org/10.1152/ajpendo.00459.2019DOI Listing

Loss of leptin receptor-expressing cells in the hindbrain decreases forebrain leptin sensitivity.

Authors:
Ruth B S Harris

Am J Physiol Endocrinol Metab 2020 May 31;318(5):E806-E816. Epub 2020 Mar 31.

Department of Physiology, Medical College of Georgia, Augusta University, Augusta, Georgia.

Previous studies indicate that inhibition of food intake by leptin is mediated by an integrated response to activation of hypothalamic and hindbrain receptors. This study tested whether loss of hindbrain leptin receptor signaling changed sensitivity to forebrain leptin. Injections of leptin-conjugated saporin (Lep-Sap) into the medial nucleus of the solitary tract (NTS) were used to destroy hindbrain leptin receptor-expressing neurons of male Sprague-Dawley rats. Read More

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http://dx.doi.org/10.1152/ajpendo.00020.2020DOI Listing

COVID-19 pandemic, coronaviruses, and diabetes mellitus.

Am J Physiol Endocrinol Metab 2020 05 31;318(5):E736-E741. Epub 2020 Mar 31.

Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.

The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. Read More

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http://dx.doi.org/10.1152/ajpendo.00124.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191633PMC

Blueberry proanthocyanidins and anthocyanins improve metabolic health through a gut microbiota-dependent mechanism in diet-induced obese mice.

Am J Physiol Endocrinol Metab 2020 Mar 31. Epub 2020 Mar 31.

Department of Medicine, Faculty of Medicine, Cardiology Axis of the Québec Heart and Lung Institute, Laval University, Hôpital Laval, Pavillon Marguerite d'Youville, Québec, QC G1V 4G5, Canada; Institute of Nutrition and Functional Foods (INAF), Laval University, 2440 boulevard Hochelaga, Québec, QC G1V 0A6.

Blueberry consumption can prevent obesity-linked metabolic diseases and it has been proposed that its polyphenol content may contribute to these effects. Polyphenols have been shown to favourably impact metabolic health, but the role of specific polyphenol classes, and whether the gut microbiota is linked to these effects remains unclear. We aimed to evaluate the impact of whole blueberry and blueberry polyphenols against the development of obesity and insulin resistance, and to determine the potential role of gut microbes in these effects by using fecal microbiota transplantation (FMT). Read More

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http://dx.doi.org/10.1152/ajpendo.00560.2019DOI Listing

The neuronal (pro)renin receptor and astrocyte inflammation in the central regulation of blood pressure and blood glucose in mice fed a high-fat diet.

Am J Physiol Endocrinol Metab 2020 May 31;318(5):E765-E778. Epub 2020 Mar 31.

Department of Pharmacology and Physiology and Cell Biology, University of Nevada, Reno, School of Medicine, Reno, Nevada.

We report here that the neuronal (pro)renin receptor (PRR), a key component of the brain renin-angiotensin system (RAS), plays a critical role in the central regulation of high-fat-diet (HFD)-induced metabolic pathophysiology. The neuronal PRR is known to mediate formation of the majority of angiotensin (ANG) II, a key bioactive peptide of the RAS, in the central nervous system and to regulate blood pressure and cardiovascular function. However, little is known about neuronal PRR function in overnutrition-related metabolic physiology. Read More

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http://dx.doi.org/10.1152/ajpendo.00406.2019DOI Listing

Downregulated microRNA-130b-5p Prevents Lipid Accumulation and Insulin Resistance in a Murine model of Nonalcoholic Fatty Liver Disease.

Am J Physiol Endocrinol Metab 2020 Mar 31. Epub 2020 Mar 31.

Department of Endocrinology, Linyi People's Hospital, Linyi 276003, P.R., China.

Nonalcoholic fatty liver disease (NAFLD) amplifies the risk of various liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis, fibrosis and cirrhosis, and ultimately hepatocellular carcinoma. Accumulating evidence suggests the involvement of aberrant microRNAs (miRNAs or miRs) in the activation of cellular stress, inflammation and fibrogenesis in hepatic cells at different stages of NAFLD and liver fibrosis. Here, we explored the potential role of miR-130b-5p in the pathogenesis of NAFLD, including lipid accumulation and insulin resistance as well as the underlying mechanism. Read More

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http://dx.doi.org/10.1152/ajpendo.00528.2019DOI Listing

--GRP94 Regulates M1 Macrophage Polarization and Insulin Resistance.

Am J Physiol Endocrinol Metab 2020 Mar 24. Epub 2020 Mar 24.

Department of Surgery, Medical University of South Carolina, Charleston; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29425, United States.

Macrophage polarization contributes to obesity-induced insulin resistance. Glucose-regulated protein 94 (GRP94) is an endoplasmic reticulum (ER) chaperon specialized for folding and quality control of secreted and membrane proteins. To determine the role of GRP94 in macrophage polarization and insulin resistance, macrophage-specific GRP94 conditional knockout (KO) mice were generated, and were challenged with high fat diet (HFD). Read More

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http://dx.doi.org/10.1152/ajpendo.00542.2019DOI Listing

The kinetics of glucagon action on the liver during insulin-induced hypoglycemia.

Am J Physiol Endocrinol Metab 2020 May 24;318(5):E779-E790. Epub 2020 Mar 24.

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.

Glucagon's effect on hepatic glucose production (HGP), under hyperglycemic conditions, is time dependent such that after an initial burst of HGP, it slowly wanes. It is not known whether this is also the case under hypoglycemic conditions, where an increase in HGP is essential. This question was addressed using adrenalectomized dogs to avoid the confounding effects of other counterregulatory hormones. Read More

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http://dx.doi.org/10.1152/ajpendo.00466.2019DOI Listing

A translation repressor, 4E-BP1, regulates the triglyceride level in rat liver during protein deprivation.

Am J Physiol Endocrinol Metab 2020 May 24;318(5):E636-E645. Epub 2020 Mar 24.

Department of Bioregulation, Institute for Advanced Medical Sciences, Nippon Medical School, Kawasaki, Kanagawa, Japan.

Protein deprivation has been shown to induce fatty liver in humans and animals, but the molecular mechanisms underlying such induction are largely unknown. Our previous studies have shown that a low-protein diet increases eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) protein and triglyceride (TG) levels in rat liver. 4E-BP1 is known to repress translation by binding to eIF4E. Read More

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http://dx.doi.org/10.1152/ajpendo.00464.2019DOI Listing

Androgen aggravates liver fibrosis by activation of NLRP3 inflammasome in CCl-induced liver injury mouse model.

Am J Physiol Endocrinol Metab 2020 May 17;318(5):E817-E829. Epub 2020 Mar 17.

College of Animal Science, Southwest University, Chongqing, China.

Studies have shown that there are differences between the sexes regarding to the occurrence and development of liver diseases, which may be associated with sex hormones. However, the mechanisms behind it are largely unknown. In this study, we first investigated the differences of liver injury between male and female mice, using the CCl-induced liver injury mouse model. Read More

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http://dx.doi.org/10.1152/ajpendo.00427.2019DOI Listing

Irisin counteracts high glucose and fatty acid-induced cytotoxicity by preserving the AMPK-insulin receptor signaling axis in C2C12 myoblasts.

Am J Physiol Endocrinol Metab 2020 May 17;318(5):E791-E805. Epub 2020 Mar 17.

Department of Surgery, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island.

Irisin, a newly identified myokine, is critical to modulating body metabolism and biological homeostasis. However, whether irisin protects the skeletal muscles against metabolic stresses remains unknown. In this study, we determine the effect of irisin on high glucose and fatty acid-induced damages using irisin-overexpressed mouse C2C12 (irisin-C2C12) myoblasts and skeletal muscle from irisin-injected mice. Read More

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http://dx.doi.org/10.1152/ajpendo.00219.2019DOI Listing
May 2020
3.785 Impact Factor

The effect of acute dual SGLT1/SGLT2 inhibition on incretin release and glucose metabolism after gastric bypass surgery.

Am J Physiol Endocrinol Metab 2020 Mar 17. Epub 2020 Mar 17.

Dept. of Endocrinology, Hvidovre Hospital, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen.

Enhanced meal-related enteroendocrine secretion, particularly of glucagon-like peptide-1 (GLP-1), contributes to weight-loss and improved glycemia after Roux-en-Y gastric bypass (RYGB). Dietary glucose drives GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion postoperatively. Understanding how glucose triggers incretin secretion following RYGB could lead to new treatments of diabetes and obesity. Read More

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http://dx.doi.org/10.1152/ajpendo.00023.2020DOI Listing

Macrophage HIF-1α mediates obesity-related adipose tissue dysfunction via interleukin-1 receptor-associated kinase M.

Am J Physiol Endocrinol Metab 2020 May 10;318(5):E689-E700. Epub 2020 Mar 10.

Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio.

Hypoxia leading to stabilization of hypoxia-inducible factor 1α (HIF-1α) serves as an early upstream initiator for adipose tissue (AT) dysfunction. Monocyte-derived macrophage infiltration in AT contributes to inflammation, fibrosis and obesity-related metabolic dysfunction. It was previously reported that myeloid cell-specific deletion of protected against high-fat diet (HFD)-induced AT dysfunction. Read More

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http://dx.doi.org/10.1152/ajpendo.00174.2019DOI Listing

Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner.

Am J Physiol Endocrinol Metab 2020 May 10;318(5):E600-E612. Epub 2020 Mar 10.

Department of Pediatrics, Division of Diabetes, Endocrinology and Metabolism, University of Michigan Medicine, Ann Arbor, Michigan.

We previously demonstrated that exposing mouse dams to metformin during gestation results in increased beta-cell mass at birth and increased beta-cell insulin secretion in adult male offspring. Given these favorable changes after a gestational maternal metformin exposure, we wanted to understand the long-term metabolic impact on offspring after exposing dams to metformin during the postnatal window. The newborn period provides a feasible clinical window for intervention and is important for beta-cell proliferation and metabolic tissue development. Read More

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http://dx.doi.org/10.1152/ajpendo.00473.2019DOI Listing

Regulation of ANGPTL8 in liver and adipose tissue by nutritional and hormonal signals and its effect on glucose homeostasis in mice.

Am J Physiol Endocrinol Metab 2020 May 10;318(5):E613-E624. Epub 2020 Mar 10.

Diabetes Division, University of Texas Health Science Center, San Antonio, Texas.

The angiopoietin-like protein (ANGPTL) family represents a promising therapeutic target for dyslipidemia, which is a feature of obesity and type 2 diabetes (T2DM). The aim of the present study was to determine the metabolic role of ANGPTL8 and to investigate its nutritional, hormonal, and molecular regulation in key metabolic tissues. The regulation of gene expression by insulin and glucose was quantified using a combination of in vivo insulin clamp experiments in mice and in vitro experiments in primary and cultured hepatocytes and adipocytes. Read More

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http://dx.doi.org/10.1152/ajpendo.00339.2019DOI Listing

Corrigendum.

Authors:

Am J Physiol Endocrinol Metab 2020 Mar;318(3):E440

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http://dx.doi.org/10.1152/ajpendo.zh1-8317-corr.2020DOI Listing

The effects of estradiol are modulated in a tissue-specific manner in mice with inducible inactivation of ERα after sexual maturation.

Am J Physiol Endocrinol Metab 2020 May 3;318(5):E646-E654. Epub 2020 Mar 3.

Centre for Bone and Arthritis Research at Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.

Mouse models with lifelong inactivation of estrogen receptor-α (ERα) show that ERα is the main mediator of estrogenic effects in bone, thymus, uterus, and fat. However, ERα inactivation early in life may cause developmental effects that confound the adult phenotypes. To address the specific role of adult ERα expression for estrogenic effects in bone and other nonskeletal tissues, we established a tamoxifen-inducible ERα-inactivated model by crossing CAGG-Cre-ER and ERα mice. Read More

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http://dx.doi.org/10.1152/ajpendo.00018.2020DOI Listing

Identification and regulation of the xenometabolite derivatives - and -3,4-methylene-heptanoylcarnitine in plasma and skeletal muscle of exercising humans.

Am J Physiol Endocrinol Metab 2020 May 26;318(5):E701-E709. Epub 2020 Feb 26.

Institute for Clinical Chemistry and Pathobiochemistry, University Hospital, Tuebingen, Germany.

Little is known about xenometabolites in human metabolism, particularly under exercising conditions. Previously, an exercise-modifiable, likely xenometabolite derivative, -3,4-methylene-heptanoylcarnitine, was reported in human plasma. Here, we identified -3,4-methylene-heptanoylcarnitine, and its -isomer, in plasma and skeletal muscle by liquid chromatography-mass spectrometry. Read More

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http://dx.doi.org/10.1152/ajpendo.00510.2019DOI Listing