Therapeutic Potential of S43126 to Treat Select Patients with Type 2 Diabetes and Hypertension

Novel therapeutic agents with reduced side‐effect profile are needed to treat type 2 diabetes. The objective of this study is to highlight the potential of a novel imidazoline compound S43126 as a future antidiabetic drug. We hypothesize that S43126 can exert beneficial effects in type 2 diabetes by a mechanism involving insulin release and insulin sensitization. Rat tail arteries were treated in a bath system with S43126 and other compounds to determine the contractile response to these agents. Control Zucker lean rats (ZLRs) and Zucker diabetic rats (ZDRs) were treated with S43126 or moxonidine for 2 weeks, and then plasma glucose and blood pressure were measured. Insulin release by mouse islets in response to varying doses of S43126 was determined. Western blot was used to determine the effect of S43126 on PKB phosphorylation. S43126 did not contract rat tail artery, but lowered blood glucose in ZDR by 31% relative to control, with no significant effect in ZLR. S43126 significantly reduce blood pressure in ZDR only. S43126 caused a dose‐dependent insulin release of up to 4 fold from mouse islet cells, only under conditions of high glucose. S43126 increased PKB phosphorylation which was blocked by efaroxan. These data suggests that S43126 decrease blood glucose by a mechanism involving insulin release, sensitization, or both. S43126 should be further studied as a possible agent to treat some patients who have type 2 diabetes and hypertension.