Chromium pretreated rats fail to develop diabetes-like symptoms after intrahypothalamic application of streptozotocin

Background: Streptozotocin (STZ) administered intraperitoneally is known to develop an animal model of type I diabetes mellitus. However, STZ injected directly into the ventromedial hypothalamic nucleus (VMH) induces various NIDDM-like feeding and metabolic alterations.

Aim: We examined whether intrahypothalamic application of Cr(III) ions could diminish the adverse effects of centrally administered STZ in male Wistar rats.

Methods: After stereotaxic surgery and a week-long recovery period, bilateral microinjection of 0.0037 M STZ (Ph 6.5–6.8) was carried out with and without chromium picolinate (2mg/ml, pH5) pretreatment. Oral glucose tolerance tests (OGTT) were carried out before the operation as well as in the acute and subacute phase (4 weeks after VMH microinjection) of our experiment. Effect of hypoglycaemia on food intake was measured 2, 4 and 24 hours after intraperitoneal insulin (0,6 IU/100g body weight) administration. Plasma insulin and leptin concentrations were measured by Rat Insulin/Leptin Ria Kit (Linco Research Inc., USA).

Results: STZ microinjection into the VMH elicited a pathological rise of blood glucose levels both in acute and subacute OGTT tests. Chromium pretreated animals did not show similar enhancement. STZ treated rats responded with a “mal-adaptive” overeating to intraperitoneal insulin injection, the Cr(III)-pretreated and control animals, however, displayed similar moderate food intake to the hypoglycemic challenge. Plasma insulin and leptin levels were found to be in the same physiologic range in all groups of rats.

Conclusion: Chromium pretreatment proved to prevent the development of homeostatic alterations elicited by STZ microinjection into the VMH.