Tissue-dependent activation of protein kinase C in fructose-induced insulin resistance.

Rats fed a fructose-enriched diet develop increases in blood pressure and resistance to insulin-mediated glucose disposal, but the underlying biochemical alterations have not been clearly defined. Since protein kinase C (PKC) has been implicated in the pathogenesis of insulin resistance, as well as blood pressure (BP) regulation, the present study was initiated to see whether changes in PKC signaling are present in rats with fructose-induced insulin resistance and hypertension. Consequently, liver, muscle, and adipose tissues were collected from fructose (n = 13) and chow (n = 12) fed Sprague-Dawley rats. PKC enzyme activity, and expression of classical PKC isozymes, were measured in cytosol and membrane fractions, and 1, 2-diacylglycerol (DAG), an endogenous stimulator of PKC, was measured by radio-enzymatic assay. Fructose feeding was associated with significant increases in fasting plasma insulin (140%) and triglyceride (400%) levels, and increased BP (20 mmHg). PKC activity was increased in the membrane fraction of adipose tissue (234 ± 38 (SE)vs 85 ± 30 pmol/min/mg protein,P< 0.007), without evidence of increased translocation or activation by DAG. Thus, fructose-induced insulin resistance has no effect on conventional PKC activity and subcellular distribution in liver and muscle, but the 3-fold increase in membraneassociated kinase activity in fat may be relevant to the mechanism of hypertriglyceridemia associated with fructose feeding.