Effect of insulin on osmoregulation of vasopressin

Patients with uncontrolled insulin-dependent diabetes mellitus have elevations in plasma vasopressin that cannot be completely accounted for by recognized stimuli. To determine whether insulin deficiency per se increases plasma vasopressin, we investigated the effect of acute insulin depletion on the osmoregulation of plasma vasopressin in insulin-dependent diabetics. When intravenous insulin infusion was stopped, plasma vasopressin, osmolality, and glucose increased over the ensuing 5 h, whereas plasma sodium decreased, and blood volume and pressure did not change. This increase in vasopressin was not due to a loss of osmoregulation, because changes in plasma osmolality and sodium, induced by infusion of hypertonic saline or water loading, induced appropriate vasopressin responses under insulin deplete as well as replete conditions. However, when plasma osmolality and glucose were raised by infusion of hypertonic dextrose, plasma vasopressin increased significantly in diabetic patients under insulin-deplete but not under insulin-replete conditions and actually decreased in healthy controls. These results indicate that acute insulin depletion increases vasopressin secretion by sensitizing the osmoreceptor to stimulation by hyperglycemia. This change in osmoreceptor specificity may be explained by postulating that glucose transport by osmoreceptor neurons as insulin dependent.