Effect of Sleep Restriction on Adipose Tissue and 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.

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Interactions between insulin and exercise

Biochemical Journal ◽

10.1042/bcj20210185 ◽

2021 ◽

Vol 478 (21) ◽

pp. 3827-3846

Author(s):

Erik A. Richter ◽

Lykke Sylow ◽

Mark Hargreaves

Keyword(s):

Physical Activity ◽

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Insulin Action ◽

Regular Exercise ◽

Fuel Storage ◽

Storage Effects ◽

Glucose Storage ◽

Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

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Effect of L-Carnitine on Insulin Sensitivity and Responsiveness in Skeletal Muscle, Adipose tissue and Hepatic tissues

Bulletin of Egyptian Society for Physiological Sciences ◽

10.21608/besps.2015.28995 ◽

2015 ◽

Vol 35 (1) ◽

pp. 46-56

Author(s):

Mohammed Adel

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity

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Hepatokine ERAP1 impairs skeletal muscle insulin sensitivity via ADRB2/PKA pathway

10.21203/rs.3.rs-37586/v1 ◽

2020 ◽

Author(s):

Feifan Guo ◽

Yuguo Niu ◽

Haizhou Jiang ◽

Hanrui Yin ◽

Fenfen Wang ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Neutralizing Antibodies ◽

Leptin Receptor ◽

Whole Body ◽

C2c12 Myotubes ◽

Insulin Resistant ◽

Skeletal Muscle Insulin Sensitivity ◽

Pka Pathway

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.

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Age-Related Decline of Skeletal Muscle Insulin Sensitivity in Rats: Effect of Sex and Muscle Type

Rejuvenation Research ◽

10.1089/rej.2010.1107 ◽

2011 ◽

Vol 14 (2) ◽

pp. 153-161 ◽

Cited By ~ 14

Author(s):

Yolanda Gómez-Pérez ◽

Magdalena Gianotti ◽

Ana M. Proenza ◽

Isabel Lladó

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Muscle Type ◽

Age Related ◽

Skeletal Muscle Insulin Sensitivity

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Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

International Journal of Molecular Sciences ◽

10.3390/ijms21041514 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1514 ◽

Cited By ~ 4

Author(s):

Paul T. Reidy ◽

Ziad S. Mahmassani ◽

Alec I. McKenzie ◽

Jonathan J. Petrocelli ◽

Scott A. Summers ◽

...

Keyword(s):

Physical Activity ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Muscle Contraction ◽

Contractile Activity ◽

Skeletal Muscle Insulin Resistance ◽

Ceramide Content ◽

Subcellular Compartmentalization ◽

Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

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Enhanced skeletal muscle insulin sensitivity after acute resistance-type exercise is upregulated by rapamycin-sensitive mTOR complex 1 inhibition

Scientific Reports ◽

10.1038/s41598-020-65397-z ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 2

Author(s):

Kohei Kido ◽

Kohei Sase ◽

Takumi Yokokawa ◽

Satoshi Fujita

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Skeletal Muscle Insulin Sensitivity ◽

Mtor Complex 1

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Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00189.2009 ◽

2009 ◽

Vol 297 (1) ◽

pp. E124-E133 ◽

Cited By ~ 85

Author(s):

Rodrigo P. A. Barros ◽

Chiara Gabbi ◽

Andrea Morani ◽

Margaret Warner ◽

Jan-Åke Gustafsson

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Glucose Homeostasis ◽

White Adipose Tissue ◽

Glucose Transporter ◽

Wild Type ◽

Glut4 Expression ◽

Glucose Challenge ◽

Fasting Hypoglycemia

Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulin-regulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)β agonists. In the present study, to investigate the relative contributions of ERα and ERβ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER−/− mice. ERβ−/− mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ERα−/− mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ERα−/− mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERβ antagonist in SM but had no effect on WAT. In ERβ−/− mice, Tam did not affect GLUT4 in SM but acted as an ERα antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERα and ERβ, ERβ-mediated repression of GLUT4 predominates in SM but ERα-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ERα predominates in WAT and ERβ in SM.

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