Classical PKC is not associated with defective insulin signaling in patients with impaired glucose tolerance

To investigate the role of insulin signaling defects in impaired glucose tolerance (IGT), we assessed the functionality of the insulin signaling cascade before and after insulin stimulation in both IGT group and control group.

Ten IGT subjects and 15 control subjects were recruited for this study. Whole-body insulin-mediated glucose uptake was determined using a euglycemic hyperinsulinemic clamp test. Muscle biopsies were obtained from the vastus lateralis muscle before and after insulin stimulation, to assess the insulin signaling cascade.

The insulin-stimulated incremental changes in phosphorylated IR-beta, IRS, Akt, and GSK-3 beta and in the membrane-associated PKC-zeta protein level were reduced in the IGT group compared with those in the control group (p<0.05). The membrane-associated PKC-lambda protein level was also reduced in the IGT group, but not significantly so (p=0.08). The incremental changes in the protein levels of PKC-alpha, -beta, and -theta were not significantly different between the two groups.

The subjects with IGT showed decreased membrane-associated PKC-zeta/lambda activity in response to insulin stimulation, as well as defects in early insulin signaling. Our results suggest that membrane-associated PKC-alpha and -beta may not be associated with insulin resistance in IGT.