Suppression by insulin treatment of glucose-induced inhibition of insulin release in non-insulin-dependent diabetics.

Although restoration of normoglycemia in non-insulin-dependent diabetic subjects improves insulin release evoked by several secretagogues, conflicting data were reported concerning the effect of intensive insulin therapy on the first-phase response of the B-cell to an intravenous glucose challenge. In the present study, 14 non-insulin-dependent diabetics underwent an intravenous glucose test performed before and after 20 h of glycemic normalization. Before insulin treatment, glucose failed, as a rule, to provoke an early positive secretory response. On the contrary, a paradoxical inhibition of insulin release was observed in most patients. This phenomenon was reproducible when a second test was performed 120 min after the first one. The paradoxical inhibition was not observed any more after glycemic normalization. As judged from the paired difference (delta) between the early increment in insulin release before and after insulin treatment, normoglycemia resulted in an improved secretory response (delta greater than 5.0 microU/ml) in seven patients, whilst the first-phase response remained little affected (delta less than 3.0 microU/ml) in the other seven subjects. These findings suggest that an impaired first-phase response to glucose does not always represent an irreversible primary defect of the pancreatic B-cell in diabetic subjects.