Glucagon Responses to Hypoglycemia in Type I Diabetic Men After 24-hour Glucoregulation by Glucose-controlled Insulin Infusion

To determine if the attenuated glucagon response to insulin-induced glucopenia characteristic of type I diabetic patients might be restored to normal by optimizing glucose “control,” four type I diabetic men were studied after precise glucoregulation by means of a glucose-controlled insulin infusion system (GCIIS). Plasma glucose and immunoreactive glucagon (IRG) levels were measured before and after an intravenous bolus of insulin, and the results were compared with those in six healthy young men and in five healthy, type I diabetic patients who were receiving conventional insulin therapy. In comparison to the augmented secretion of IRG in the normals after glucopenia, the conventionally treated diabetic subjects had a trivial increase in IRG levels despite similar decrements in plasma glucose levels. In four diabetic men, plasma glucose levels were maintained within euglycemic ranges by GCIIS throughout 24 h, and, immediately thereafter, their IRG responses to insulin-evoked hypoglycemia were quantitatively indistinguishable from the type I diabetic patients who had not been treated by GCIIS. These observations contrast to evidence that A-cell responses to signals such as glucose or amino acids are partially or completely restored by short- or long-term insulin administration. It is inferred that this abnormality reflecting a possible defect in A-cell glucose recognition may be a persistent abnormality in patients with type I diabetes.