Presentation description

During hypoglycemic events, the body detects and secretes the counterregulatory hormone glucagon from pancreatic alpha cells to raise blood glucose levels back to normal. However, people with diabetes lose the ability to secrete glucagon within a few years after diabetes onset, making them more susceptible to experiencing hypoglycemia stemming from insulin treatment. The mechanism underlying this loss is not known, but may be linked to chronically elevated somatostatin levels which can suppress glucagon secretion. Therefore, somatostatin receptor blockers may have therapeutic potential to help restore glucagon secretion in people with diabetes and lessen the burden of hypoglycemia. A novel somatostatin receptor 2 antagonist, ZT-01, exhibited good efficacy when given subcutaneously, but the treatment required multiple daily injections which is less appealing. Hence, the current study aimed to evaluate whether ZT-01 retains its efficacy when chronically administered to type 1 diabetic rats through subcutaneous osmotic pumps. The animals were treated with one of three different doses of ZT-01: 0.288, 1.15 and 1.32mg/day. Our data showed that when compared to the vehicle-treated group, ZT-01 was most effective in enhancing glucagon secretion in type 1 diabetic rats at the 1.15 and 1.32mg/d doses (P<0.05), while the lowest dose showed no effect. We therefore conclude that long-term subcutaneous delivery of ZT-01 may be a viable therapeutic option to help restore glucagon secretion in type 1 diabetes.