Role of insulin in the abnormal glucagon secretory response to hypoglycemia in type 1 diabetes

Iatrogenic hypoglycemia is the main limiting factor of insulin treatment in Type 1 Diabetes Mellitus (T1DM). The deficient glucagon counterregulation in response to therapeutic insulin-induced hypoglycemia is classical, but the mechanism is poorly understood. We hypothesized that in those patients exogenous insulin may suppress glucagon secretion from the alpha cell, but the alpha cell may still be normal. This hypothesis was tested in the current study on the spontaneously diabetic Biobreeding/Worcester (BB) rats using a hypoinsulinemic glucose clamp technique. Our results showed a marked plasma glucagon response to hypoglycemia during the hypoinsulinemic glucose clamp but not by insulin. We concluded that impaired glucagon secretion during insulin-induced hypoglycemia in the T1DM patients is due to a suppressive effect of exogenous insulin on the a-cell and is not an irreversible defect.