ALTERED GLUCAGON AND PHOSPHOENOLPYRUVATE CARBOXY-KINASE ACTIVITY (PEPCK) IN THE HYPOGLYCEMIC GROWTH RETARDED NEWBORN RAT

Abstract

The role of insulin and glucagon in causing hypoglycemia in the growth retarded neonate is not well-understood. These hormones not only directly regulate glucose availability but also affect enzyme induction. Glucagon induces PEPCK, a key gluco-neogenic enzyme, while insulin inhibits its induction. We studied newborn rat pups whose mothers had undergone bilateral uterine artery ligation (L), sham (S), or no surgery (N). L pups were significantly smaller than S and N pups and were hypoglycemic at birth, 20, and 240 minutes but had values comparable to S and N pups at 60 and 120 minutes. L pups had significantly reduced hepatic glycogen concentrations. Plasma insulin was low and did not differ at any time between groups. Glucagon in L pups significantly exceeded S and N values at 20 and 60 minutes (60 min: L 641±106; S 217±31; N 318±28 pg/ml; p <.01). PEPCK increased significantly in S and N but not L pups by 240 minutes (L .14±.03; S .26±.05; N .24±.03 μmoles PEP/g liver/min; p<.01). Glucagon administrated to L pups at birth significantly increased PEPCK by 240 minutes. In L pups, hypoglycemia does not exaggerate the normal decrease in insulin. Deficient glycogen is responsible for the initial hypoglycemia while diminished gluconeogenesis due to limited glucagon induction of PEPCK is responsible for the later hypoglycemia. Diminished sensitivity to glucagon may be responsible for delayed PEPCK induction in L pups.

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