Mechanisms Causing Insulin Resistance in Obesity

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Although the mechanisms that cause insulin resistance in muscle are not known with certainty, there appear to be some generally accepted concepts that form the basis of a model that serves as the basis for future hypothesis testing. In response to either TNFa or intramuscular lipids (fatty acyl-CoA, diacylglycerol, or ceram-ides), there is activation of a serine kinase (PKC, JNK, or IkKP) and inactivation of a protein phosphatase (PP2A), such that IRS-1 and the insulin receptor become serine phosphorylated. These events then depress insulin-signal transduction to cause insulin resistance. Figure 5.1 displays a representation of insulin signaling in a muscle cell.

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