Effects Of Sustained Release Somatostatin Type 2 Antagonism On Glucagon Counterregulation And Glycemia In Type 2 Diabetic Rate Model

This thesis examined whether a novel somatostatin receptor 2 antagonist (SSTR2a), ZT-01, could enhance endogenous glucagon secretion and protect against hypoglycemia in a rat model of type 2 diabetes (T2D). Male Sprague Dawley rats were placed on a high-fat diet and injected with streptozotocin to induce T2D. The rats were then chronically treated with varying doses of ZT-01 or vehicle using implanted mini-osmotic pumps. While ZT-01 did not significantly affect basal glucose levels or oral glucose tolerance, it tended to increase baseline glucagon levels and the glucagon response to insulin-induced hypoglycemia, though the effects were small. Overall, sustained exposure to SSTR2a modestly improved the glucose and glucagon response to insulin-induced hypoglycemia in this T2D model, suggesting the potential for this approach to prevent hypoglycemia in insulin-requiring T2D.