LOSS OF THE HEPATIC GLYCOGEN-BINDING SUBUNIT (G(L)) OF PROTEIN PHOSPHATASE-1 UNDERLIES DEFICIENT GLYCOGEN-SYNTHESIS IN INSULIN-DEPENDENT DIABETIC RATS AND IN ADRENALECTOMIZED STARVED RATS

Hepatic glycogen synthesis is impaired in insulin-dependent diabetic r ats and in adrenalectomized starved rats, and although this is known t o be due to defective activation of glycogen synthase by glycogen synt hase phosphatase, the underlying molecular mechanism has not been deli neated. Glycogen synthase phosphatase comprises the catalytic subunit of protein phosphatase 1 (PP1) complexed with the hepatic glycogen-bin ding subunit, termed G(L). In liver extracts of insulin-dependent diab etic and adrenalectomized starved rats, the level of G(L) was shown by immunoblotting to be substantially reduced compared with that in cont rol extracts, whereas the level of PP1 catalytic subunit was not affec ted by these treatments. Insulin administration to diabetic rats resto red the level of G(L) and prolonged administration raised it above the control levels, whereas re-feeding partially restored the G(L) level in adrenalectomized starved rats. The regulation of G(L) protein level s by insulin and starvation/ feeding was shown to correlate with chang es in the level of the G(L) mRNA, indicating that the long-term regula tion of the hepatic glycogen-associated form of PP1 by insulin, and he nce the activity of hepatic glycogen synthase, is predominantly mediat ed through changes in the level of the G(L) mRNA.