Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α

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FIG. 4.
FIG. 4.

Hypothetical schema to explain changes in DAG, PKC, and IκB-α associated with insulin resistance in muscle of humans infused with lipid during a euglycemic-hyperinsulinemic clamp. Key initiating events are an increase in plasma FFA, which elevates the cytosolic concentration of long-chain fatty acyl CoA (LCCoA), and an increased uptake into muscle of glucose. The latter enhances glycerolipid (TG, DAG) synthesis both by generating α-glycerophosphate and by enhancing the synthesis of malonyl CoA, which inhibits fatty acid oxidation by mitochondria. It is assumed that activation of PKC sets in motion changes in IκB-α and NFκB by one or more of the indicated mechanisms; however, direct proof that it does so in human muscle is lacking (see text). The precise events that lead to insulin resistance remain to be determined. IKKB, IκB kinase.

This Article

  1. Diabetes vol. 51 no. 7 2005-2011