Peripherally administered KP-10 prevents development of insulin-induced hypoglycemic shock in diabetic rhesus monkeys

Abstract

This study investigated whether kisspeptin-10 (KP-10) prevents diabetic rhesus monkeys from insulin-induced hypoglycemic shock. Thirty-six adult male rhesus monkeys were used, six in each group. Diabetes was induced with streptozotocin (45mg/kg b.w.; single dose i.v.). Groups were as: saline control, insulin alone, pre-insulin (treated with KP-10, 30 min before insulin), post-insulin (treated with KP-10, 30min after insulin), treated with premix dose of KP-10 (50μg) and insulin, and the group treated with the kisspeptin antagonist P234 (50μg). Following an overnight fast, each animal was subjected to respective treatment, and blood glucose concentrations were recorded every 30-min interval for 3h. Intergroup comparisons demonstrated that treatment with KP-10 prior to insulin administration and kisspeptin-insulin premix treatment allowed blood glucose levels to rise to significantly higher levels (p < 0.001) by 180min in diabetic and healthy animals compared to treatment with insulin alone. However, intragroup comparisons revealed a significant decrease in blood glucose level in diabetic animals only. Treatment with P234 antagonist followed by insulin administration abolished the preventive action of kisspeptin, whereby blood glucose decreased significantly (p < 0.001) in both diabetic and healthy animals. KP-10 post-insulin treatment, however, remained ineffective and led, instead, to significantly decreased glucose concentrations by 180min in both diabetic and healthy animals when compared to animals treated with insulin alone. KP-10 bears therapeutic potential to prevent hypoglycemic shock that may sometimes occur during intensive insulin therapy. Several pharmacological aspects of its interaction with insulin and other drugs, however, remain to be investigated.