scholarly journals A Molecular and Whole Body Insight of the Mechanisms Surrounding Glucose Disposal and Insulin Resistance with Hypoxic Treatment in Skeletal Muscle

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
R. W. A. Mackenzie ◽  
P. Watt
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Control ◽  
Direct Action ◽  
Acute Hypoxia ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hypoxic Exposure ◽  
Obstructive Sleep

Although the mechanisms are largely unidentified, the chronic or intermittent hypoxic patterns occurring with respiratory diseases, such as chronic pulmonary disease or obstructive sleep apnea (OSA) and obesity, are commonly associated with glucose intolerance. Indeed, hypoxia has been widely implicated in the development of insulin resistance either via the direct action on insulin receptor substrate (IRS) and protein kinase B (PKB/Akt) or indirectly through adipose tissue expansion and systemic inflammation. Yet hypoxia is also known to encourage glucose transport using insulin-dependent mechanisms, largely reliant on the metabolic master switch, 5′ AMP-activated protein kinase (AMPK). In addition, hypoxic exposure has been shown to improve glucose control in type 2 diabetics. The literature surrounding hypoxia-induced changes to glycemic control appears to be confusing and conflicting. How is it that the same stress can seemingly cause insulin resistance while increasing glucose uptake? There is little doubt that acute hypoxia increases glucose metabolism in skeletal muscle and does so using the same pathway as muscle contraction. The purpose of this review paper is to provide an insight into the mechanisms underpinning the observed effects and to open up discussions around the conflicting data surrounding hypoxia and glucose control.

Prevention of skeletal muscle insulin resistance by dietary cod protein in high fat-fed rats

2001 ◽  
Vol 281 (1) ◽  
pp. E62-E71 ◽  
Author(s):  
Charles Lavigne ◽  
Frédéric Tremblay ◽  
Geneviève Asselin ◽  
Hélène Jacques ◽  
André Marette
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Amino Acids ◽  
Glucose Uptake ◽  
Soy Protein ◽  
Whole Body ◽  
Glucose Disposal ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

In the present study, we tested the hypothesis that fish protein may represent a key constituent of fish with glucoregulatory activity. Three groups of rats were fed a high-fat diet in which the protein source was casein, fish (cod) protein, or soy protein; these groups were compared with a group of chow-fed controls. High-fat feeding led to severe whole body and skeletal muscle insulin resistance in casein- or soy protein-fed rats, as assessed by the euglycemic clamp technique coupled with measurements of 2-deoxy-d-[3H]glucose uptake rates by individual tissues. However, feeding cod protein fully prevented the development of insulin resistance in high fat-fed rats. These animals exhibited higher rates of insulin-mediated muscle glucose disposal that were comparable to those of chow-fed rats. The beneficial effects of cod protein occurred without any reductions in body weight gain, adipose tissue accretion, or expression of tumor necrosis factor-α in fat and muscle. Moreover, L6 myocytes exposed to cod protein-derived amino acids showed greater rates of insulin-stimulated glucose uptake compared with cells incubated with casein- or soy protein-derived amino acids. These data demonstrate that feeding cod protein prevents obesity-induced muscle insulin resistance in high fat-fed obese rats at least in part through a direct action of amino acids on insulin-stimulated glucose uptake in skeletal muscle cells.

scholarly journals Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle

Diabetologia ◽  
2021 ◽  
Author(s):  
Theresia Sarabhai ◽  
Chrysi Koliaki ◽  
Lucia Mastrototaro ◽  
Sabine Kahl ◽  
Dominik Pesta ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Insulin Signalling ◽  
Whole Body ◽  
Glucose Disposal ◽  
Diabetes Research ◽  
German Research Foundation ◽  
Development Fund ◽  
Before And After

Abstract Aims/hypothesis Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. Methods In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. Results SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). Conclusions/interpretation Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. Trial registration ClinicalTrials.gov.NCT01736202. Funding German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research. Graphical abstract

scholarly journals Polycystic Ovary Syndrome Is Associated with Tissue-Specific Differences in Insulin Resistance

2009 ◽  
Vol 94 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Theodore P. Ciaraldi ◽  
Vanita Aroda ◽  
Sunder Mudaliar ◽  
R. Jeffrey Chang ◽  
Robert R. Henry
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Polycystic Ovary ◽  
Whole Body ◽  
Glucose Disposal ◽  
Signaling Proteins ◽  
Impaired Insulin ◽  
Isolated Adipocytes ◽  
Insulin Responsiveness

Abstract Objective: The potential differential contributions of skeletal muscle and adipose tissue to whole body insulin resistance were evaluated in subjects with polycystic ovary syndrome (PCOS). Research Design and Methods: Forty-two PCOS subjects and 15 body mass index-matched control subjects were studied. Insulin action was evaluated by the hyperinsulinemic/euglycemic clamp procedure. Isolated adipocytes and cultured muscle cells were analyzed for glucose transport activity; adipocytes, muscle tissue, and myotubes were analyzed for the expression and phosphorylation of insulin-signaling proteins. Results: Fifty-seven per cent of the PCOS subjects had impaired glucose tolerance and the lowest rate of maximal insulin-stimulated whole body glucose disposal compared to controls (P &lt; 0.01). PCOS subjects with normal glucose tolerance had intermediate reduction in glucose disposal rate (P &lt; 0.05 vs. both control and impaired glucose tolerance subjects). However, rates of maximal insulin-stimulated glucose transport (insulin responsiveness) into isolated adipocytes were comparable between all three groups, whereas PCOS subjects displayed impaired insulin sensitivity. In contrast, myotubes from PCOS subjects displayed reduced insulin responsiveness for glucose uptake and normal sensitivity. There were no differences between groups in the expression of glucose transporter 4 or insulin-signaling proteins or maximal insulin stimulation of phosphorylation of Akt in skeletal muscle, myotubes, or adipocytes. Conclusions: Individuals with PCOS display impaired insulin responsiveness in skeletal muscle and myotubes, whereas isolated adipocytes display impaired insulin sensitivity but normal responsiveness. Skeletal muscle and adipose tissue contribute differently to insulin resistance in PCOS. Insulin resistance in PCOS cannot be accounted for by differences in the expression of selected signaling molecules or maximal phosphorylation of Akt.

scholarly journals High-Fat Diet-Mediated Lipotoxicity and Insulin Resistance Is Related to Impaired Lipase Expression in Mouse Skeletal Muscle

Endocrinology ◽  
2013 ◽  
Vol 154 (4) ◽  
pp. 1444-1453 ◽  
Author(s):  
Pierre-Marie Badin ◽  
Isabelle K. Vila ◽  
Katie Louche ◽  
Aline Mairal ◽  
Marie-Adeline Marques ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Protein Content ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Whole Body ◽  
Wild Type ◽  
High Fat ◽  
Lipase Expression

Abstract Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cϵ membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P &lt; .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (−37%, P &lt; .05) and AS160 Thr642 (−47%, P &lt;.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice.

Insulin sensitivity is preserved despite disrupted endothelial function

2006 ◽  
Vol 291 (4) ◽  
pp. E691-E696 ◽  
Author(s):  
Sudha S. Shankar ◽  
Robert V. Considine ◽  
J. Christopher Gorski ◽  
Helmut O. Steinberg
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Endothelial Dysfunction ◽  
Glucose Uptake ◽  
Vascular Function ◽  
Separate Group ◽  
Whole Body ◽  
Glucose Disposal ◽  
Significant Impairment ◽  
Hiv Negative

It is well established that endothelial dysfunction and insulin resistance go hand in hand. However, it is unclear whether endothelial dysfunction per se is sufficient to impair insulin-mediated glucose uptake. We have previously reported that 4 wk of administration of the human immunodeficiency virus (HIV)-1 protease inhibitor indinavir to HIV-negative subjects induces endothelial dysfunction. Hence, we hypothesized that indinavir-induced endothelial dysfunction was associated with impaired insulin-mediated glucose disposal. We measured insulin-mediated glucose disposal at the level of the whole body, skeletal muscle, and vasculature by performing hyperinsulinemic euglycemic clamp, and vascular function studies, in a separate group of HIV-negative healthy nonobese subjects ( n = 13) before and after 4 wk of daily oral indinavir. Four weeks of indinavir resulted in a 113 ± 29% ( P < 0.01) reduction of endothelium-dependent vasodilation, consistent with our earlier findings. In addition, there was a significant impairment of insulin-mediated vasodilation (101 ± 14% before indinavir vs. 35 ± 15% after indinavir; P < 0.05). However, there was no significant change in insulin-mediated glucose disposal at the level of the whole body (8.9 ± 0.5 before indinavir vs. 8.5 ± 0.6 mg·kg−1·min−1after indinavir; P = 0.4), or skeletal muscle. Furthermore, in a separate group of four HIV-negative healthy nonobese subjects, we found that 4 wk of indinavir has no sustained effect on insulin-stimulated glucose uptake in adipose tissue. Thus our findings indicate that 1) endothelial dysfunction alone is insufficient to impair insulin-mediated glucose disposal, and 2) indinavir-induced endothelial dysfunction is likely due to a direct effect of the drug on the endothelium and is not coupled to the induction of insulin resistance.

scholarly journals Perioperative Infusion of Glucagon-Like Peptide-1 Prevents Insulin Resistance After Surgical Trauma in Female Pigs

Endocrinology ◽  
2019 ◽  
Vol 160 (12) ◽  
pp. 2892-2902
Author(s):  
Martin Hagve ◽  
Petter F Gjessing ◽  
Mikal J Hole ◽  
Kirsten M Jansen ◽  
Ole Martin Fuskevåg ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Whole Body ◽  
Glucose Disposal ◽  
Control Group ◽  
Surgical Trauma ◽  
Glucose Release ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Insulin resistance is an independent negative predictor of outcome after elective surgery and increases mortality among surgical patients in intensive care. The incretin hormone glucagon-like peptide-1 (GLP-1) potentiates glucose-induced insulin release from the pancreas but may also increase insulin sensitivity in skeletal muscle and directly suppress hepatic glucose release. Here, we investigated whether a perioperative infusion of GLP-1 could counteract the development of insulin resistance after surgery. Pigs were randomly assigned to three groups; surgery/control, surgery/GLP-1, and sham/GLP-1. Both surgery groups underwent major abdominal surgery. Whole-body glucose disposal (WGD) and endogenous glucose release (EGR) were assessed preoperatively and postoperatively using D-[6,6-2H2]-glucose infusion in combination with hyperinsulinemic euglycemic step-clamping. In the surgery/control group, peripheral insulin sensitivity (i.e., WGD) was reduced by 44% relative to preoperative conditions, whereas the corresponding decline was only 9% for surgery/GLP-1 (P < 0.05). Hepatic insulin sensitivity (i.e., EGR) remained unchanged in the surgery/control group but was enhanced after GLP-1 infusion in both surgery and sham animals (40% and 104%, respectively, both P < 0.05). Intraoperative plasma glucose increased in surgery/control (∼20%) but remained unchanged in both groups receiving GLP-1 (P < 0.05). GLP-1 diminished an increase in postoperative glucagon levels but did not affect skeletal muscle glycogen or insulin signaling proteins after surgery. We show that GLP-1 improves intraoperative glycemic control, diminishes peripheral insulin resistance after surgery, and suppresses EGR. This study supports the use of GLP-1 to prevent development of postoperative insulin resistance.

Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications

2013 ◽  
Vol 304 (5) ◽  
pp. E453-E465 ◽  
Author(s):  
Nicolas J. Pillon ◽  
Philip J. Bilan ◽  
Lisbeth N. Fink ◽  
Amira Klip
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Cross Talk ◽  
Immune Cells ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Whole Body ◽  
Glucose Disposal ◽  
Muscle Inflammation ◽  
Anti Inflammatory

Skeletal muscles contain resident immune cell populations and their abundance and type is altered in inflammatory myopathies, endotoxemia or different types of muscle injury/insult. Within tissues, monocytes differentiate into macrophages and polarize to acquire pro- or anti-inflammatory phenotypes. Skeletal muscle macrophages play a fundamental role in repair and pathogen clearance. These events require a precisely regulated cross-talk between myofibers and immune cells, involving paracrine/autocrine and contact interactions. Skeletal muscle also undergoes continuous repair as a result of contractile activity that involves participation of myokines and anti-inflammatory input. Finally, skeletal muscle is the major site of dietary glucose disposal; therefore, muscle insulin resistance is essential to the development of whole body insulin resistance. Notably, muscle inflammation is emerging as a potential contributor to insulin resistance. Recent reports show that inflammatory macrophage numbers within muscle are elevated during obesity and that muscle cells in vitro can mount autonomous inflammatory responses under metabolic challenge. Here, we review the nature of skeletal muscle inflammation associated with muscle exercise, damage, and regeneration, endotoxin presence, and myopathies, as well as the new evidence of local inflammation arising with obesity that potentially contributes to insulin resistance.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

Whole body insulin resistance in rat offspring of mothers consuming alcohol during pregnancy or lactation: comparing prenatal and postnatal exposure

2004 ◽  
Vol 96 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Li Chen ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Resistance ◽  
Birth Weight ◽  
Glucose Tolerance ◽  
The Body ◽  
Whole Body ◽  
Glucose Disposal ◽  
Tolerance Index ◽  
Sensitivity Index ◽  
Intravenous Glucose ◽  
Rat Offspring

This study examined the effects of maternal ethanol (EtOH) consumption during pregnancy or lactation on glucose homeostasis in the adult rat offspring. Glucose disposal was determined by minimal model during an intravenous glucose tolerance test in rats that had a small or normal birth weight after EtOH exposure in utero and in rats whose mothers were given EtOH during lactation only. All three EtOH groups had decreased glucose tolerance index and insulin sensitivity index, but their glucose effectiveness was not different from that of controls. In addition, EtOH rat offspring that were small at birth had elevated plasma, liver, and muscle triglyceride levels. The data show that EtOH exposure during pregnancy programs the body to insulin resistance later in life, regardless of birth weight, but that this effect also results in dyslipidemia in growth-restricted rats. In addition, insulin resistance is also evident after EtOH exposure during lactation.

Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

2014 ◽  
Vol 307 (10) ◽  
pp. E885-E895 ◽  
Author(s):  
Marjolein A. Wijngaarden ◽  
Leontine E. H. Bakker ◽  
Gerard C. van der Zon ◽  
Peter A. C. 't Hoen ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Lipid Oxidation ◽  
Energy Homeostasis ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Metabolic Adaptation ◽  
Protein Kinase Activity ◽  
Short Term ◽  
Muscle Energy

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

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