Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Dec 30;2:112.
doi: 10.3389/fphys.2011.00112. eCollection 2011.

The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise

Affiliations
Free PMC article

The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise

Jørgen Jensen et al. Front Physiol. .
Free PMC article

Abstract

Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g). Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycemic clamp, 70-90% of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen's main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake ([Formula: see text]) and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new "fight or flight" events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes.

Keywords: de novo lipogenesis; exercise; glycogen phosphorylase; glycogen synthase; insulin resistance; type 2 diabetes.

Figures

Figure 1
Figure 1
Insulin signaling pathways regulating glucose transport and glycogen synthase in skeletal muscle. Insulin activates protein kinase B (PKB) through phosphatidylinositol 3-kinase (PI3K) and two upstream kinases; namely phosphoinositide-dependent protein kinase-1 (PDK1; phosphorylates PKB at threonine 308) and the mammalian target of rapamycin complexed with Rictor (mTORC2; phosphorylates PKB at serine 473). The activated PKB phosphorylates Akt substrate of 160 kDa (AS160, also called TBC1D4) and TBC1D1, which inhibits Rab GTPase activity and promotes GTP binding to Rabs, thereby allowing GLUT4 translocation. For glycogen synthesis, the activated PKB phosphorylates glycogen synthase kinase-3 (GSK3), which leads to inhibition of GSK3 activity and subsequently dephosphorylation and activation of glycogen synthase (GS). IRS, insulin receptor substrate; PIP2, phosphatidylinositol 4,5-biphosphate; PIP3, phosphatidylinositol 3,4,5-trisphosphate; G, glucose.
Figure 2
Figure 2
Excess energy intake is stored after meals as glycogen and triacylglycerols. Carbohydrate can be stored as glycogen mainly in skeletal muscles or the liver; fat is manly stores as triacylglycerol in adipose tissue. With filled glycogen stores, glucose can be the substrate for de novo lipid synthesis and stored in adipocytes, muscles, or the liver and cause insulin resistance. Glycogen and fat are important energy substrates during exercise.

Similar articles

See all similar articles

Cited by 62 articles

See all "Cited by" articles

References

    1. Aas V., Rokling-Andersen M., Wensaas A. J., Thoresen G. H., Kase E. T., Rustan A. C. (2005). Lipid metabolism in human skeletal muscle cells: effects of palmitate and chronic hyperglycaemia. Acta Physiol. Scand. 183, 31–4110.1111/j.1365-201X.2004.01381.x - DOI - PubMed
    1. Acheson K. J., Schutz Y., Bessard T., Anantharaman K., Flatt J. P., Jequier E. (1988). Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man. Am. J. Clin. Nutr. 48, 240–247 - PubMed
    1. Alessi D. R., Cohen P. (1998). Mechanism of activation and function of protein kinase B. Curr. Opin. Genet. Dev. 8, 55–6210.1016/S0959-437X(98)80062-2 - DOI - PubMed
    1. Arias E. B., Kim J., Funai K., Cartee G. D. (2007). Prior exercise increases phosphorylation of Akt substrate of 160 kDa (AS160) in rat skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 292, E1191–E120010.1152/ajpendo.00602.2006 - DOI - PubMed
    1. Aslesen R., Engebretsen E. M. L., Franch J., Jensen J. (2001). Glucose uptake and metabolic stress in rat muscles stimulated electrically with different protocols. J. Appl. Physiol. 91, 1237–1244 - PubMed

LinkOut - more resources

Feedback