IN-VIVO EFFECTS OF GLUCOSE AND INSULIN ON SECRETION AND GENE-EXPRESSION OF GLUCAGON IN RATS

We investigated the effects of insulin and glucose on the control of s ecretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglyc emia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemi a plus hyperinsulinemia; EG-HI rats), and 2) a prolonged postinfusion period in both groups. In HG-HI rats, elevation of plasma insulin and glucose concentrations by about 7 and 5 times, respectively, resulted in a decline in glucagon levels, which fell significantly within 6 h a nd remained low thereafter, whereas these levels were unchanged in EG- HI rats. Glucagon messenger RNA levels and pancreatic glucagon content were not significantly affected in either HG-HI or EG-HI rats. After cessation of infusions, hypoglycemia occurred in both group of rats. I n HG-HI rats, hypoglycemia lasted for about 36 h without any surge in the plasma glucagon level, whereas in EG-HI rats it was transient (sim ilar to 1 h) and stimulated glucagon secretion. In both groups the pan creatic or-cell was unresponsive to arginine during the postinfusion p eriod. In conclusion, although a role of intraislet insulin cannot be excluded, glucagon gene expression is insensitive to changes in plasma glucose and insulin concentrations. In contrast, hyperglycemia/hyperi nsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the a-cell responsiveness to hypoglycemia.