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 ra ts (C) or diabetic rats (DM), respectively. Following insulin treatmen t for DM, insulin resistance was clearly reversed. Phospholipase C (PL C) caused a 4-fold increase in lipogenesis in C, but not in DM. Insuli n 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 PL C-stimulated PKC activity. 5'-Guanylylimidodiphosphate (Gpp(NH)p) exer ted a stimulatory effect on diacylglycerol (DAG) generation in permeab ilized adipocytes from C, but not in DM. Insulin treatment partially r estored the stimulatory effect of Gpp(NH)p. These findings suggest tha t a particular G protein(s) is involved in the regulation of DAG gener ation in adipocytes, and that diabetes leads to a functional or quanti tative abnormality in G protein and G protein-PLC. Insulin therapy par tially restored G protein-PLC dependent glucose uptake.