scholarly journals Improvement of obesity-linked skeletal muscle insulin resistance by strength and endurance training

2017 ◽  
Vol 234 (3) ◽  
pp. R159-R181 ◽  
Author(s):  
Sergio Di Meo ◽  
Susanna Iossa ◽  
Paola Venditti
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Endurance Training ◽  
Glucose Transport ◽  
Antioxidant Defenses ◽  
Metabolic Dysfunction ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance

Obesity-linked insulin resistance is mainly due to fatty acid overload in non-adipose tissues, particularly skeletal muscle and liver, where it results in high production of reactive oxygen species and mitochondrial dysfunction. Accumulating evidence indicates that resistance and endurance training alone and in combination can counteract the harmful effects of obesity increasing insulin sensitivity, thus preventing diabetes. This review focuses the mechanisms underlying the exercise role in opposing skeletal muscle insulin resistance-linked metabolic dysfunction. It is apparent that exercise acts through two mechanisms: (1) it stimulates glucose transport by activating an insulin-independent pathway and (2) it protects against mitochondrial dysfunction-induced insulin resistance by increasing muscle antioxidant defenses and mitochondrial biogenesis. However, antioxidant supplementation combined with endurance training increases glucose transport in insulin-resistant skeletal muscle in an additive fashion only when antioxidants that are able to increase the expression of antioxidant enzymes and/or the activity of components of the insulin signaling pathway are used.

Restoring AS160 phosphorylation rescues skeletal muscle insulin resistance and fatty acid oxidation while not reducing intramuscular lipids

2009 ◽  
Vol 297 (5) ◽  
pp. E1056-E1066 ◽  
Author(s):  
Hakam Alkhateeb ◽  
Adrian Chabowski ◽  
Jan F. C. Glatz ◽  
Brendon Gurd ◽  
Joost J. F. P. Luiken ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Transport ◽  
Acid Oxidation ◽  
Glut4 Translocation ◽  
Muscle Insulin Resistance ◽  
Palmitate Oxidation ◽  
Skeletal Muscle Insulin Resistance ◽  
Ampk Phosphorylation ◽  
Intramuscular Lipids

We examined whether AICAR or leptin rapidly rescued skeletal muscle insulin resistance via increased palmitate oxidation, reductions in intramuscular lipids, and/or restoration of insulin-stimulated AS60 phosphorylation. Incubation with palmitate (2 mM, 0–18 h) induced insulin resistance in soleus muscle. From 12–18 h, palmitate was removed or AICAR or leptin was provided while 2 mM palmitate was maintained. Palmitate oxidation, intramuscular triacylglycerol, diacylglycerol, ceramide, AMPK phosphorylation, basal and insulin-stimulated glucose transport, plasmalemmal GLUT4, and Akt and AS160 phosphorylation were examined at 0, 6, 12, and 18 h. Palmitate treatment (12 h) increased intramuscular lipids (triacylglycerol +54%, diacylglycerol +11%, total ceramide +18%, C16:0 ceramide +60%) and AMPK phosphorylation (+118%), whereas it reduced fatty acid oxidation (−60%) and insulin-stimulated glucose transport (−70%), GLUT4 translocation (−50%), and AS160 phosphorylation (−40%). Palmitate removal did not rescue insulin resistance or associated parameters. The AICAR and leptin treatments did not consistently reduce intramuscular lipids, but they did rescue palmitate oxidation and insulin-stimulated glucose transport, GLUT4 translocation, and AS160 phosphorylation. Increased AMPK phosphorylation was associated with these improvements only when AICAR and leptin were present. Hence, across all experiments, AMPK phosphorylation did not correlate with any parameters. In contrast, palmitate oxidation and insulin-stimulated AS160 phosphorylation were highly correlated ( r = 0.83). We speculate that AICAR and leptin activate both of these processes concomitantly, involving activation of unknown kinases in addition to AMPK. In conclusion, despite the maintenance of high concentrations of palmitate (2 mM), as well as increased concentrations of intramuscular lipids (triacylglycerol, diacylglycerol, and ceramide), the rapid AICAR- and leptin-mediated rescue of palmitate-induced insulin resistance is attributable to the restoration of insulin-stimulated AS160 phosphorylation and GLUT4 translocation.

scholarly journals Irisin and Myonectin Regulation in the Insulin Resistant Muscle: Implications to Adipose Tissue: Muscle Crosstalk

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Luis Gamas ◽  
Paulo Matafome ◽  
Raquel Seiça
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Current Knowledge ◽  
Fatty Acid Uptake ◽  
Acid Uptake ◽  
Vicious Cycle ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance

Myokines are peptides produced and secreted by the skeletal muscle, with autocrine, paracrine, and endocrine actions. Many of them are overexpressed during physical exercise and appear to contribute to the benefits of exercise to metabolic homeostasis. Irisin, resulting from the cleavage of the membrane protein FNDC5, was shown to induce adipocyte browning, with increased lipid oxidation and thermogenesis. Myonectin was only recently discovered and initial studies revealed a role in fatty acid uptake and oxidation in adipose tissue and liver. However, the mechanisms of their regulation by exercise are not entirely established. Impaired secretion and action of myokines, such as irisin and myonectin, may have a role in the establishment of insulin resistance. On the other hand, several studies have shown that insulin resistance in the skeletal muscle may change myokines expression and secretion. This may have consequences on lipid and glucose metabolism in adipose tissue and lead to a vicious cycle between impaired myokines production and insulin resistance. This review summarizes the current knowledge about the influence of skeletal muscle insulin resistance on the secretion of irisin and myonectin, as well as its impact on adipose tissue metabolism.

scholarly journals Skeletal Muscle Insulin Resistance and Absence of Inflammation Characterize Insulin-Resistant Grade I Obese Women

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0154119 ◽  
Author(s):  
Cacylde Amouzou ◽  
Cyril Breuker ◽  
Odile Fabre ◽  
Annick Bourret ◽  
Karen Lambert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Obese Women ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance

Correction of diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance by moderate hyperleptinemia

2000 ◽  
Vol 278 (3) ◽  
pp. E563-E569 ◽  
Author(s):  
Roland Buettner ◽  
Christopher B. Newgard ◽  
Christopher J. Rhodes ◽  
Robert M. O'Doherty
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Plasma Glucose ◽  
Metabolic Abnormalities ◽  
High Fat ◽  
Human Obesity ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance ◽  
Plasma Leptin

Human obesity and high fat feeding in rats are associated with the development of insulin resistance and perturbed carbohydrate and lipid metabolism. It has been proposed that these metabolic abnormalities may be reversible by interventions that increase plasma leptin. Up to now, studies in nongenetic animal models of obesity and in human obesity have concentrated on multiple injection therapy with mixed results. Our study sought to determine whether a sustained, moderate increase in plasma leptin, achieved by administration of a recombinant adenovirus containing the leptin cDNA (AdCMV-leptin) would be effective in reversing the metabolic abnormalities of the obese phenotype. Wistar rats fed a high-fat diet (HF) were heavier ( P< 0.05), had increased fat mass and intramuscular triglycerides (mTG), and had elevated plasma glucose, insulin, triglyceride, and free fatty acids compared with standard chow-fed (SC) control animals (all P < 0.01). HF rats also had impaired glucose tolerance and were markedly insulin resistant, as demonstrated by a 40% reduction in insulin-stimulated muscle glucose uptake ( P < 0.001). Increasing plasma leptin levels to 29.0 ± 1.5 ng/ml (from 7.0 ± 1.4 ng/ml, P < 0.001) for a period of 6 days decreased adipose mass by 40% and normalized plasma glucose and insulin levels. In addition, insulin-stimulated skeletal muscle glucose uptake was normalized in hyperleptinemic rats, an effect that correlated closely with a 60% ( P < 0.001) decrease in mTG. Importantly, HF rats that received a control adenovirus containing the β-galactosidase cDNA and were calorically matched to AdCMV-leptin-treated animals remained hyperglycemic, hyperinsulinemic, insulin resistant, and maintained elevated mTG. We conclude that a gene-therapeutic intervention that elevates plasma leptin moderately for a sustained period reverses diet-induced hyperglycemia, hyperinsulinemia, and skeletal muscle insulin resistance, and that these improvements are tightly linked to leptin-induced reductions in mTG.

Cytosolic lipid excess-induced mitochondrial dysfunction is the cause or effect of high fat diet-induced skeletal muscle insulin resistance: a molecular insight

2018 ◽  
Vol 46 (1) ◽  
pp. 957-963 ◽  
Author(s):  
Baishali Alok Jana ◽  
Pavan Kumar Chintamaneni ◽  
Praveen Thaggikuppe Krishnamurthy ◽  
Ashish Wadhwani ◽  
Suresh Kumar Mohankumar
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
High Fat Diet ◽  
High Fat ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

scholarly journals Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner

2015 ◽  
Vol 308 (8) ◽  
pp. E662-E669 ◽  
Author(s):  
Lisette A. Maddison ◽  
Kaitlin E. Joest ◽  
Ryan M. Kammeyer ◽  
Wenbiao Chen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Blood Glucose ◽  
Glucose Tolerance ◽  
Fasting Blood Glucose ◽  
Β Cells ◽  
Β Cell ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance

Insulin resistance creates an environment that promotes β-cell failure and development of diabetes. Understanding the events that lead from insulin resistance to diabetes is necessary for development of effective preventional and interventional strategies, and model systems that reflect the pathophysiology of disease progression are an important component toward this end. We have confirmed that insulin enhances glucose uptake in zebrafish skeletal muscle and have developed a zebrafish model of skeletal muscle insulin resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted insulin signaling and glucose uptake in the skeletal muscle, confirming insulin resistance. In young animals, we observed an increase in the number of β-cells and normal glucose tolerance that was indicative of compensation for insulin resistance. In older animals, the β-cell mass was reduced to that of control with the appearance of impaired glucose clearance but no elevation in fasting blood glucose. Combined with overnutrition, the insulin-resistant animals have an increased fasting blood glucose compared with the control animals, demonstrating that the β-cells in the insulin-resistant fish are in a vulnerable state. The relatively slow progression from insulin resistance to glucose intolerance in this model system has the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets.

scholarly journals Activation of the Hexosamine Signaling Pathway in Adipose Tissue Results in Decreased Serum Adiponectin and Skeletal Muscle Insulin Resistance

Endocrinology ◽  
2004 ◽  
Vol 145 (5) ◽  
pp. 2118-2128 ◽  
Author(s):  
Mark Hazel ◽  
Robert C. Cooksey ◽  
Deborah Jones ◽  
Glendon Parker ◽  
John L. Neidigh ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Serum Adiponectin ◽  
Glucose Disposal ◽  
Mrna Levels ◽  
Muscle Insulin Resistance ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Resistance

Abstract Overexpression of the rate-limiting enzyme for hexosamine synthesis (glutamine:fructose-6-phosphate amidotransferase) in muscle and adipose tissue of transgenic mice was previously shown to result in insulin resistance and hyperleptinemia. Explanted muscle from transgenic mice was not insulin resistant in vitro, suggesting that muscle insulin resistance could be mediated by soluble factors from fat tissue. To dissect the relative contributions of muscle and fat to hexosamine-induced insulin resistance, we overexpressed glutamine:fructose-6-phosphate amidotransferase 2.5-fold, specifically in fat under control of the aP2 promoter. Fasting glucose, insulin, and triglycerides were unchanged in the transgenic mice; leptin and β-hydroxybutyrate levels were 91% and 29% higher, respectively. Fasted transgenic mice have mild glucose intolerance and skeletal muscle insulin resistance in vivo. In fasting transgenic mice, glucose disposal rates with hyperinsulinemia were decreased 27% in females and 10% in males. Uptake of 2-deoxy-d-glucose into muscle was diminished by 45% in female and 21% in male transgenics. Serum adiponectin was also lower in the fasted transgenics, by 37% in females and 22% in males. TNFα and resistin mRNA levels in adipose tissue were not altered in the fasted transgenics; levels of mRNA for leptin were increased and peroxisome proliferator-activated receptor γ decreased. To further explore the relationship between adiponectin and insulin sensitivity, we examined mice that have been refed for 6 h after a 24-h fast. Refeeding wild-type mice resulted in decreased serum adiponectin and increased leptin. In transgenic mice, however, the regulation of these hormones by refeeding was lost for adiponectin and diminished for leptin. Refed transgenic female and male mice no longer exhibited decreased serum adiponectin in the refed state, and they were no longer insulin resistant as by lower or unchanged insulin and glucose levels. We conclude that increased hexosamine levels in fat, mimicking excess nutrient delivery, are sufficient to cause insulin resistance in skeletal muscle. Changes in serum adiponectin correlate with the insulin resistance of the transgenic animals.

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