Presenter: Chantelle Yazzie
Authors: Chantelle Yazzie, Irvane Nelson, Owen Chan
Faculty Advisor: Owen Chan
Institution: Utah Valley University
Loss of the ability to secrete glucagon in individuals with Type 1 diabetes (T1D) places them at greater risk for experiencing hypoglycemia or “low blood sugars”, which is a major problem for those patients placed on intensive insulin therapy. While the reason underlying this loss is not known, one mechanism that has been proposed is the increase in somatostatin secretion that is observed in T1D. As somatostatin normally inhibits glucagon secretion, blocking its actions may be one potential therapeutic strategy to help restore the glucagon response to hypoglycemia in T1D patients. We previously showed that the novel somatostatin receptor 2 antagonist, ZT-01, exhibited good efficacy in restoring glucagon responses to hypoglycemia in two-week, poorly controlled streptozotocin-diabetic rats, when given subcutaneously one hour prior to hypoglycemia onset. The goal of the current study was to determine the ideal dose timing strategy for ZT-01. We examined the efficacy of ZT-01 when administered either 3 or 6 hours prior to the induction of hypoglycemia (45±5mg/dl) using a hyperinsulinemic-hypoglycemic clamp. Our initial data shows that ZT-01 enhances glucagon secretion to hypoglycemia when given 3 hours prior to the induction of hypoglycemia compared to vehicle-treated diabetic animals (VEH: 62±8, ZT-01: 156±41, P<0.05), but the efficacy is lost when given 6 hours prior to hypoglycemia induction (VEH: 78±16, ZT-01: 87±15, P=NS). In conclusion, antagonism of type 2 somatostatin receptors with ZT-01 may be a promising therapy to restore glucagon secretion in diabetic patients when given up to three hours prior hypoglycemia onset.