Insulin secretory responses to both oral and intravenous glucose were investigated in 12 nonobese noninsulin-dependent diabetic subjects before and after strict metabolic control of blood glucose levels without weight loss. Glycemic control was achieved by applying an artificial pancreas to all diabetics for 2 or 3 days, which led to restoration of normal fasting blood glucose levels and to significant reduction of fasting plasma insulin (p less than 0.01) and C-peptide (p less than 0.05) levels. Initially, the insulin response to oral glucose was weak and delayed, but increased significantly after treatment (p less than 0.01), although none of the diabetic subjects achieved completely normal glucose tolerance. The i.v. glucose tolerance test (0.33 g/kg) revealed that all diabetics lacked acute insulin response in the basal state with low glucose disappearance rates (0.37 +/- 0.07 %/min). After 48h of normoglycemia, these figures did not change significantly, although the insulinogenic index (insulin area/glucose area) was significantly increased (p less than 0.05). A marked increase in both phases of insulin secretion was evident when a larger intravenous glucose pulse (0.66 g/kg) was used in some diabetics in order to raise the blood glucose concentrations of the post-treatment test to those of the pre-treatment test. In absolute terms, the insulin responses of the post-treatment tests were not significantly different from those of sex-, age- and weight-matched control subjects, but were significantly lower if related to the corresponding plasma glucose responses (insulinogenic index lower than that of controls). These studies in nonobese noninsulin-dependent diabetic subjects indicate that glycemic control with an artificial pancreas improves insulin response to glucose, suggesting that chronic hyperglycemia may stress the impaired B-cell secretory capacity of diabetes.