The Link Between Adipose Tissue and Skeletal Muscle Insulin Resistance

2008 ◽  
Vol 40 (Supplement) ◽  
pp. 49
Author(s):  
David Dyck
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

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 Intermuscular adipose tissue directly modulates skeletal muscle insulin sensitivity in humans

2019 ◽  
Vol 316 (5) ◽  
pp. E866-E879 ◽  
Author(s):  
Stephan Sachs ◽  
Simona Zarini ◽  
Darcy E. Kahn ◽  
Kathleen A. Harrison ◽  
Leigh Perreault ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Matrix Proteins ◽  
Muscle Insulin Resistance ◽  
Intermuscular Adipose Tissue ◽  
Skeletal Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Sensitivity

Intermuscular adipose tissue (IMAT) is negatively related to insulin sensitivity, but a causal role of IMAT in the development of insulin resistance is unknown. IMAT was sampled in humans to test for the ability to induce insulin resistance in vitro and characterize gene expression to uncover how IMAT may promote skeletal muscle insulin resistance. Human primary muscle cells were incubated with conditioned media from IMAT, visceral (VAT), or subcutaneous adipose tissue (SAT) to evaluate changes in insulin sensitivity. RNAseq analysis was performed on IMAT with gene expression compared with skeletal muscle and SAT, and relationships to insulin sensitivity were determined in men and women spanning a wide range of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Conditioned media from IMAT and VAT decreased insulin sensitivity similarly compared with SAT. Multidimensional scaling analysis revealed distinct gene expression patterns in IMAT compared with SAT and muscle. Pathway analysis revealed that IMAT expression of genes in insulin signaling, oxidative phosphorylation, and peroxisomal metabolism related positively to donor insulin sensitivity, whereas expression of macrophage markers, inflammatory cytokines, and secreted extracellular matrix proteins were negatively related to insulin sensitivity. Perilipin 5 gene expression suggested greater IMAT lipolysis in insulin-resistant individuals. Combined, these data show that factors secreted from IMAT modulate muscle insulin sensitivity, possibly via secretion of inflammatory cytokines and extracellular matrix proteins, and by increasing local FFA concentration in humans. These data suggest IMAT may be an important regulator of skeletal muscle insulin sensitivity and could be a novel therapeutic target for skeletal muscle insulin resistance.

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.

scholarly journals NF-κB-Inducing Kinase (NIK) Mediates Skeletal Muscle Insulin Resistance: Blockade by Adiponectin

Endocrinology ◽  
2011 ◽  
Vol 152 (10) ◽  
pp. 3622-3627 ◽  
Author(s):  
Sanjeev Choudhary ◽  
Sandeep Sinha ◽  
Yanhua Zhao ◽  
Srijita Banerjee ◽  
Padma Sathyanarayana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Uptake ◽  
Kinase Activity ◽  
Pi3 Kinase ◽  
Dominant Negative ◽  
Muscle Insulin Resistance ◽  
Akt Phosphorylation ◽  
Skeletal Muscle Insulin Resistance ◽  
Obese Subjects

Enhanced levels of nuclear factor (NF)-κB-inducing kinase (NIK), an upstream kinase in the NF-κB pathway, have been implicated in the pathogenesis of chronic inflammation in diabetes. We investigated whether increased levels of NIK could induce skeletal muscle insulin resistance. Six obese subjects with metabolic syndrome underwent skeletal muscle biopsies before and six months after gastric bypass surgery to quantitate NIK protein levels. L6 skeletal myotubes, transfected with NIK wild-type or NIK kinase-dead dominant negative plasmids, were treated with insulin alone or with adiponectin and insulin. Effects of NIK overexpression on insulin-stimulated glucose uptake were estimated using tritiated 2-deoxyglucose uptake. NF-κB activation (EMSA), phosphatidylinositol 3 (PI3) kinase activity, and phosphorylation of inhibitor κB kinase β and serine-threonine kinase (Akt) were measured. After weight loss, skeletal muscle NIK protein was significantly reduced in association with increased plasma adiponectin and enhanced AMP kinase phosphorylation and insulin sensitivity in obese subjects. Enhanced NIK expression in cultured L6 myotubes induced a dose-dependent decrease in insulin-stimulated glucose uptake. The decrease in insulin-stimulated glucose uptake was associated with a significant decrease in PI3 kinase activity and protein kinase B/Akt phosphorylation. Overexpression of NIK kinase-dead dominant negative did not affect insulin-stimulated glucose uptake. Adiponectin treatment inhibited NIK-induced NF-κB activation and restored insulin sensitivity by restoring PI3 kinase activation and subsequent Akt phosphorylation. These results indicate that NIK induces insulin resistance and further indicate that adiponectin exerts its insulin-sensitizing effect by suppressing NIK-induced skeletal muscle inflammation. These observations suggest that NIK could be an important therapeutic target for the treatment of insulin resistance associated with inflammation in obesity and type 2 diabetes.

Lowered extracellular pH is involved in the pathogenesis of skeletal muscle insulin resistance

2014 ◽  
Vol 445 (1) ◽  
pp. 170-174 ◽  
Author(s):  
Hiroki Hayata ◽  
Hiroaki Miyazaki ◽  
Naomi Niisato ◽  
Noriko Yokoyama ◽  
Yoshinori Marunaka
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Extracellular Ph ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance

Reversal of chronic alterations of skeletal muscle protein kinase C from fat-fed rats by BRL-49653

1997 ◽  
Vol 273 (5) ◽  
pp. E915-E921 ◽  
Author(s):  
Carsten Schmitz-Peiffer ◽  
Nicholas D. Oakes ◽  
Carol L. Browne ◽  
Edward W. Kraegen ◽  
Trevor J. Biden
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Muscle Protein ◽  
Skeletal Muscle Protein ◽  
Insulin Sensitizer ◽  
Muscle Insulin Resistance ◽  
Skeletal Muscle Insulin Resistance ◽  
Kinase C

We have recently shown that the reduction in insulin sensitivity of rats fed a high-fat diet is associated with the translocation of the novel protein kinase Cε(nPKCε) from cytosolic to particulate fractions in red skeletal muscle and also the downregulation of cytosolic nPKCθ. Here we have further investigated the link between insulin resistance and PKC by assessing the effects of the thiazolidinedione insulin-sensitizer BRL-49653 on PKC isoenzymes in muscle. BRL-49653 increased the recovery of nPKC isoenzymes in cytosolic fractions of red muscle from fat-fed rats, reducing their apparent activation and/or downregulation, whereas PKC in control rats was unaffected. Because BRL-49653 also improves insulin-stimulated glucose uptake in fat-fed rats and reduces muscle lipid storage, especially diglyceride content, these results strengthen the association between lipid availability, nPKC activation, and skeletal muscle insulin resistance and support the hypothesis that chronic activation of nPKC isoenzymes is involved in the generation of muscle insulin resistance in fat-fed rats.

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.

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