Glucagon and Perinatal Metabolism in the Rat

Abstract

In the rat, plasma glucagon levels rise and plasma insulin falls immediately after birth. The changes in the levels of pancreatic hormones precede the development of liver glycogenolysis and gluconeogenesis. Several lines of evidence support the role of glucagon in these hepatic adaptations: (a) The rise of glucagon precedes the hepatic changes concomitant with an increase in liver 3′5′ cyclic AMP. (b) Exogenous glucagon injected into a fetal rat is capable of provoking premature liver glycogenolysis and gluconeogenesis in vivo and in vitro. (c) The intracellular mediator of glucagon in the liver, 3′5′ cyclic AMP, can reproduce the metabolic effects of the hormone in fetal rat. (d) A dramatic fall of plasma gluconeogenic substrates (lactate, amino acids) occurs at birth, and exogenous glucagon increases lactate and amino acid utilization in perinatal rats. Evidence is also presented that glucagon increases hepatic amino acid uptake and liver transaminase activities. All these metabolic effects of glucagon can be antagonized by insulin, and it is proposed that the fall of insulin at birth could also contribute to the metabolic adaptation of the newborn rat. The physiological role of glucagon during fetal and neonatal life is discussed.