Beta Cell Dysfunction in Maturity-Onset Diabetes: Reversible Loss of Glucose-Induced Insulin Secretion with Retention of Response to Arginine

Abstract

While spontaneous recovery from severe diabetes is an unusual event, weight reduction and restriction of carbohydrate intake in maturity-onset diabetes often leads to satisfactory control and improvement in endogenous insulin secretion in response to a glucose load (1–3). Furthermore, infusions of insulin sufficient to induce normoglycemia in mild maturity-onset diabetics for 40–60 hours result in enhanced endogenous insulin responses to intravenous glucose (4). Since the beta cell recovers its ability to secrete insulin when hyperglycemia is relieved by such interventions, it has been suggested that hyperglycemia itself might contribute to the decreased insulin secretion which characterizes overt maturity-onset diabetes (3). In an attempt to elucidate the mechanism of insulin secretory failure in maturity-onset diabetes we have investigated glucose and arginine-induced insulin secretion before and after weight loss. The findings indicate that recent-onset fasting hyperglycemia is characterized by a failure of the beta cell to secrete insulin in response to glucose, while the response to arginine stimulation is retained. This failure of beta cell function can be substantially improved by periods of a low carbohydrate hypocaloric diet.