Effect of a novel biphenyl compound, VMNS2e on ob/ob mice

Abstract

VMNS2e is a novel biphenyl compound, which in previous studies had showed most favourable interactions with the active site of protein tyrosine phosphatase 1B (PTP1B). The effect of acute and chronic treatment of VMNS2e (30mg/kg) was investigated in ob/ob mice. Plasma glucose was measured after acute administration of VMNS2e (30mg/kg) in both lean and ob/ob mice. In the chronic study, VMNS2e (30mg/kg) was given orally, once daily for 60days. Metformin (300mg/kg) was taken as standard therapy. Body weight, food intake and blood glucose was measured weekly while glycosylated hemoglobin A(1c) (HbA(1c)), insulin, triglyceride, total cholesterol, low density lipoprotein (LDL), fructosamine, non esterified fatty acid and organ weight were estimated after the completion of treatment period. Oral glucose tolerance test was performed on the last day of treatment. Liver and epididymal fat weights were taken. Acute dose of VMNS2e elicited an anti hyperglycemic effect. It reduced blood glucose by 14% (0.5h) and 35.6% (6h). Chronic VMNS2e treatment improved glucose tolerance by 25.3%. It decreased blood glucose levels. Hyperinsulinemia was reduced (19.6%). VMNS2e treatment had no significant effect on body weight and food consumption. VMNS2e treatment exhibited significant reduction (28.2%) in HbA(1c), plasma triglyceride (49%), LDL (24%) and fructosamine (13%) levels. VMNS2e treatment did not alter total cholesterol and non esterified fatty acid levels. Epididymal fat/body weight ratio was reduced (26.3%). VMNS2e exhibited both acute and chronic anti hyperglycemic effect, insulin sensitivity along with improvement in various lipid parameters and glycemic control.