Glucagon Secretion by Dispersed Alpha Cell Enriched Islets from Streptozotocin Treated Hamsters in Perifusion

Summary

Streptozotocin (70 mg/kg) was administered intravenously to female Syrian hamsters. The hamsters received insulin (5U/animal/day). Insulin treatment was withdrawn 3 days before sacrifice in one group, while another group was maintained on insulin until sacrifice. Ten to 14 days following Streptozotocin administration the animals were killed, and the pancreatic islets isolated and subsequently dispersed. Islet DNA content was decreased while the glucagon content was elevated by Streptozotocin treatment. The glucagon secretory responsiveness of the dispersed alpha cells of control animals was stimulated by glucopenia and decreased by glucose. Alpha cells of Streptozotocin hamsters were not only suppressed but were actually stimulated by high glucose concentrations. Treatment with insulin in vivo but not in vitro, resulted in a restoration of the alpha cells responsiveness to glucose suppression. Dispersed alpha cells from control and Streptozotocin treated animals were stimulated by arginine. Basal and total glucagon secretion was greatest in dispersed alpha cells from Streptozotocin treated animals. We concluded: that the paradoxical response of alpha cells to glucose noted in diabetes is not due to short term insulin deprivation or the lack of morphologic contact with beta cells; that the alpha cells require an insulin stimulated islet metabolite and extra islet materials to respond appropriately to glucose; and that the alpha cells response to arginine is mediated independently of glucose regulation.

Key-Words:

Glucagon - Alpha Cell Response - Streptozotocin Diabetes