Insulin, pyruvate dehydrogenase

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Pyruvate dehydrogenase T T CoA, NAD insulin, ADP, pyruvate Acetyl-CoA, NADH, ATP (fatty acids, ketone bodies)... 

Insulin stimulates lipogenesis by several other mechanisms as well as by increasing acetyl-CoA carboxylase activity. It increases the transport of glucose into the cell (eg, in adipose tissue), increasing the availability of both pyruvate for fatty acid synthesis and glycerol 3-phosphate for esterification of the newly formed fatty acids, and also converts the inactive form of pyruvate dehydrogenase to the active form in adipose tissue but not in liver. Insulin also—by its ability to depress the level of intracellular cAMP—inhibits lipolysis in adipose tissue and thereby reduces the concentration of... 

Nakai, N., Y. Sato, Y. Oshida, N. Fujitsuka, A. Yoshimura, and Y. Shimomura (1999). Insulin activation of pyruvate dehydrogenase complex is enhanced by exercise training. Metabolism Clin. Exper. 48 865-869. 

Pyruvate dehydrogenase, especially in the adipose tissue, is stimulated by a high insulin/glucagon ratio. This leads to the production of acetyl-CoA, which may enter the Krebs cycle in the fed state. The more likely possibility is the biosynthesis of fatty acids from acetyl-CoA. The latter requires NADPH, and for this reason, the hexose monophosphate shunt is also activated. 

Insulin is an antilipolytic hormone, and its effect on adipose tissue is to increase the transport of glucose into the fat cell, to stimulate lipogenesis and inhibit lipolysis. Thus, pyruvate dehydrogenase and acetyl-CoA carboxylase are activated, and the hormone-sensitive lipase is inactivated. In the normal, well-fed state insulin stimulates the deposition of fat. 

Pyruvate dehydrogenase phosphatase (PDH) assay was determined using the method of Caro (1). The effects of selected experimental agents in stimulating the insulin-dependent enzyme PDH at 100 and 0.1 p,M, 1.0 and 10pM are provided in Tables 1 and 2, respectively. 

Lamer, J., Huang, L.C., Schwartz, C.EW., Oswald, A.S., Shen, T.-Y., Kinter, M., Tang, G., and Zeller, K., 1988, Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphatase contains galatosamine and D-chiroinositol. Biochem. Biophys. Res. Commun. 151 1416-1426. 

Hnang B, Wn P, Bowker-Kinley MM, and Harris RA (2002) Regnlation of pyruvate dehydrogenase kinase expression hy peroxisome proliferator-activated receptor-alpha ligands, glucocorticoids, and insulin. Diabetes 51,276-83. 

Sugden MC, Bulmer K, Augustine D, and Holness MJ (2001a) Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha implications for glucose-stimulated insulin secretion. Diabetes 50, 2729-36. 

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