Beneficial effects of kinin B1 receptor antagonism on plasma fatty acid alterations and obesity in Zucker diabetic fatty rats

Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia.