Lack of the stimulatory effect of guanine nucleotide on diacylglycerol generation in permeabilized adipocytes from diabetic rats.

Insulin caused an 8- or a 3-fold increase in lipogenesis in control rats (C) or diabetic rats (DM), respectively. Following insulin treatment for DM, insulin resistance was clearly reversed. Phospholipase C (PLC) caused a 4-fold increase in lipogenesis in C, but not in DM. Insulin treatment partially restored PLC-induced lipogenesis. Insulin or PLC increased protein kinase C (PKC) activity in the membrane fraction in C, but not in DM. Insulin treatment partially restored insulin- or PLC-stimulated PKC activity. 5'-Guanylylimidodiphosphate (Gpp(NH)p) exerted a stimulatory effect on diacylglycerol (DAG) generation in permeabilized adipocytes from C, but not in DM. Insulin treatment partially restored the stimulatory effect of Gpp(NH)p. These findings suggest that a particular G protein(s) is involved in the regulation of DAG generation in adipocytes, and that diabetes leads to a functional or quantitative abnormality in G protein and G protein-PLC. Insulin therapy partially restored G protein-PLC dependent glucose uptake.