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 carbohydrate (HC) milk formula in their infancy were used for this study and compared with mother-fed (MF) controls.

MEASUREMENTS

Glycogen, glycogen synthase, protein phosphatase-1 (PP-1), mitogen-activated protein kinase (MAPK), insulin-stimulated protein kinase (ISPK) and protein kinase A (PKA) were measured in liver and muscle of both MF and HC rats.

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 activities of both MAPK and ISPK were also decreased in the HC rats. In contrast PKA activity was increased.

CONCLUSIONS

Glycogen synthase activity in the basal state may be impaired in the hyperinsulinemic HC rats in two ways: (i) by a decrease in the activities of the kinases that presumably activate PP-1 and (ii) by increased activity of PKA which inactivates glycogen synthase directly by phosphorylation and indirectly by its effects on PP-1.