Responses of the pancreatic A cell during hypoglycemia and hyperglycemia are dependent on the B cell

It is controversial whether stimulation of glucagon secretion by hypoglycemia or suppression by hyperglycemia is a direct effect of glucose on the A cell or whether it is mediated indirectly through the B cell. To determine the role of the B cell in the mediation of glucagon secretion adolescent male baboons were studied before and after successive injections of streptozocin designed to cause B-cell destruction in a series of stages. Following one dose of streptozocin, B-cell function was impaired but fasting blood glucose remained normal. B-cell function declined further with additional doses of streptozocin. As B-cell function declined, there was a corresponding reduction in the glucagon response to hypoglycemia (G hyp). There were significant correlations between the percentage reduction in G hyp and the percentage reduction in B-cell function (acute insulin response to arginine, r = .47; acute insulin response to glucose, r = .69; K g, r = .79). In a second study the ability of hyperglycemia to suppress the acute glucagon response to arginine (AGR arg) was studied. Before streptozocin AGR arg was 128 ± 26 pg/mL at a glucose level of 80 ± 4 mg/dL and was suppressed to 74 ± 20 pg/mL when glucose was raised and clamped at 209 ± 14 mg/dL. After the initial dose of streptozocin, with mild B cell damage and fasting normoglycemia, AGR arg was not suppressed by hyperglycemia. With severe B cell dysfunction and fasting hyperglycemia, there was paradoxical enhancement of AGR arg by additional hyperglycemia. In conclusion, the ability of the A cell to respond appropriately to hypoglycemia and to arginine during hyperglycemia is dependent on normal B-cell function.