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 secretion and gene expression of glucagon in vivo in rats. Animals were studied during 1) a 48-h period of either glucose infusion (hyperglycemia plus hyperinsulinemia; HG-HI rats) or insulin infusion (euglycemia 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 and 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. In 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 (similar to 1 h) and stimulated glucagon secretion. In both groups the pancreatic or-cell was unresponsive to arginine during the postinfusion period. 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/hyperinsulinemia, not hyperinsulinemia alone, lowers glucagon secretion and affects the a-cell responsiveness to hypoglycemia.