Streptozotocin Diabetes-Induced Hyperadrenal Corticoidism: Central Mechanisms

Abstract

Streptozotocin (STZ)-induced diabetic rats were used to evaluate possible central mechanisms responsible for the chronic hyperadrena/corticoidism present in diabetics. To achieve this goal, both basal levels and K+-stimulated release of the adrenocorticotropin (ACTH) secretagogues, corticotropin releasing factor (CRF) and arginine vasopressin (AVP), were measured from mediobasal hypothalamus (MBH) or median eminence (ME) tissues, respectively, obtained from diabetic or control animals. MBH epinephrine (EPI) concentrations were measured to evaluate whether changes in CRF might be mediated through central EPI neurons. The ability of insulin replacement therapy to reverse any diabetic-related changes was also evaluated. STZ caused a severe state of diabetes as evidenced by large increases in daily water intake, decreased body weight and increased blood glucose levels compared to vehicle-treated control animals. The concentration of CRF, but not AVP or EPI, was decreased in diabetic animals. Although the basal release of CRF or AVP was not altered by diabetes, the K+-stimulated release of CRF was enhanced in diabetic animals compared to that seen in vehicle treated animals. The K+-stimulated release of AVP from ME tissues was similar in both STZ- and vehicle-treated animals. Insulin replacement therapy successfully reversed the polydipsia and hyperglycemia resulting from STZ injection, and completely reversed the diabetes-induced changes in CRF content and release. The data provide evidence that diabetes results in a selective hypersecretion of central CRF in response to normal stimulatory inputs which may be responsible, in part, for the hyperadrenalcorticoidism observed in diabetics.