GPR119 Agonism Increases Glucagon Secretion During Insulin-Induced Hypoglycemia

• DOI: 10.2337/db18-0031
• Publication Date: 2018-04-18T15:02:42Z
• Authors: Nina Xiaoyan Li; Stacey Brown; Tim Kowalski; Margaret Wu; Liming Yang; Ge Dai; Aleksandr Petrov; Yuyan Ding; Tamara Dlugos; Harold B. Wood; Liangsu Wang; Mark Erion; Robert Sherwin; David E. Kelley
• Keywords: Incretin

Insulin-induced hypoglycemia in diabetes is associated with impaired glucagon secretion. In this study, we tested whether stimulation of GPR119, a G-protein–coupled receptor expressed pancreatic islet as well enteroendocrine cells and previously shown to stimulate insulin incretin secretion, might enhance secretion during hypoglycemia. the GPR119 agonists were applied isolated islets or perfused pancreata assess hypoglycemic hyperglycemic conditions. Insulin infusion clamps performed without agonist pretreatment counterregulation healthy streptozotocin (STZ)-induced diabetic rats, including those exposed recurrent bouts insulin-induced that leads suppression hypoglycemia-induced release. Hypoglycemic clamp studies also conducted knockout (KO) mice evaluate pharmacological stimulatory actions on an on-target effect. The results revealed agonist-treated cultured had increased low glucose perfusion. vivo, significantly STZ-diabetic response was absent KO mice. addition, counterregulatory responses restored by rats antecedent Thus, have ability pharmacologically augment specifically rodents. Whether effect serve diminish occurrence severity iatrogenic intensive therapy patients remains be established.