Insulin resistance kinase

Itani SI, Ruderman NB, Schmieder F and Boden G. 2002. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and IkappaB-alpha. Diabetes 51(7) 2005-2011. 

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, Ye JM, Lee CH, Oh WK, Kim CT, Hohnen-Behrens C, Gosby A, Kraegen EW, James DE, Kim JB. (2006) Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistance states. Diabetes 55 2256-2264. 

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Um SH, D Alessio D, Thomas G. Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell. Metab. 2006 3 393-102. 

Elmendorf, J. S., 0amran-Abney, A., Smith, T, David, T and Turinsky, J. (1997), Phospha-tidylinositol 3-kinase and dynamics of insulin resistance in denervated slow and fast muscles in e Jlxj. Am.. Physjcf, Z72, E661-E670,... 

The above may be of pathophysiological relevance as a decreased basal and insulin-stimulated glycogen phosphatase activity and phosphorylase phosphatase activity (Type-1 protein phosphatase, PP-1) in the skeletal muscle of insulin-resistant individuals has been found (Freymond era/., 1988 Kida era/., 1990, 1992 Damsbo et al., 1991). Other studies suggest increased phosphotyrosine phosphatase activity in patients with NIDDM who show decreased autoactivation of the insulin receptor kinase (McGuire et al., 1991). 

Insulin resistance, in particular in skeletal muscle, plays a pivotal role in the pathogenesis of NIDDM. Several abnormalities of the insulin-signalling chain have been found. At the receptor level a decreased tyrosine kinase activity has been described which appears to be due to a regulatory event (reviewed by Haring, 1991). Relevant mutations of the insulin receptor were not found (reviewed by Haring and Mehnert, 1993). Abnormalities at the level of glycogen synthase were observed as discussed above. There is also some... 

The reduction in receptors may be a secondary consequence of hyper-glycaemia and hyperinsulinaemia and does not relate well to the impairment of insulin action. It therefore seems unlikely that a defect in the number or affinity of insulin receptors is a primary abnormality in NIDDM. However, it is possible that an abnormality of the portion of the insulin receptor projecting into the cell (/3-subunit) could contribute to insulin resistance. Tyrosine kinase activity of the /3-subunit appears to be intimately involved in mediating insulin action this tyrosine kinase activity is reduced in some animal models of diabetes and there is some evidence that the same is true in human NIDDM. 

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