GLYCOGEN-SYNTHASE REGULATION IN HYPERINSULINEMIC OBESE PROGENY OF RATS FED A HIGH-CARBOHYDRATE FORMULA IN THEIR INFANCY/

OBJECTIVE: To evaluate the effects of chronic hyperinsulinemia/obesity on the proximal events leading to the activation of glycogen synthase . DESIGN: 100 d old second generation of chronically hyperinsulinemic/ obese rats born to mothers which were artificially reared on a high ca rbohydrate (HC) milk formula in their infancy were used for this study and compared with mother-fed (MF) controls. MEASUREMENTS: Glycogen, g lycogen synthase, protein phosphatase-1 (PP-1), mitogen-activated prot ein kinase (MARK), insulin-stimulated protein kinase (ISPK) and protei n kinase A (PKA) were measured in liver and muscle of both MF and HC r ats. RESULTS: Glycogen content, glycogen synthase and PP-1 activities were significantly reduced in liver and muscle of HC rats compared to MF controls while trypsin released PP-1 activity was elevated. The act ivities of both MAPK and ISPK were also decreased in the HC rats. In c ontrast PKA activity was increased. CONCLUSIONS: Glycogen synthase act ivity in the basal state may be impaired in the hyperinsulinemic HC ra ts in two ways: (i) by a decrease in the activities of the kinases tha t presumably activate PP-1 and (ii) by increased activity of PKA which inactivates glycogen synthase directly by phosphorylation and indirec tly by its effects on PP-1.