Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia.

The present study assessed the effects of γ-aminobutyric acid (GABA) from β-cells on glucose levels and glucagon secretion, and identified channels via which glucagon secretion is initiated. An in vivo experiment was performed containing three groups: Intrapancreatic artery infusion of GABA alone, GABA plus insulin or insulin alone in rats with diabetes. Rats infused with GABA and insulin were also subdivided in groups receiving additional infusion of K+-channel activator diazoxide (DIA), K+-channel blocker tolbutamide (TLB) and calcium channel blocker nifedipine (NIF). In the hypoglycemic state, termination of infusion of insulin and insulin plus GABA resulted in signaling to the α-cells to secrete glycogen, while that of GABA alone did not. However, intrapancreatic artery infusion of K+-channel activator DIA, K+-channel blocker TLB or calcium channel blocker NIF in addition to GABA and insulin had no effect on glucagon secretion. In conclusion, if the delivery of insulin or GABA plus insulin in rats with hypoglycemia is terminated, β-cells are stimulated and signal the α-cells to secrete glucagon. Thus, the detection of a sudden decrease in zinc levels by β-cells as well as a decrease in GABA in the periportal circulation induces signaling to α-cells to stimulate them to secrete glucagon.