Calcitonin and Omega-3 Fatty Acids Exhibit Antagonistic and Non-Additive Effects in Experimental Diabetes

Because optimising therapy for the management of diabetes mellitus remains challenging, the study investigated the effects of salmon calcitonin (Sct) and/or omega-3 fatty acids (N-3 - eicosapentaenoic acid and docosahexaenoic acid-3:2), compared to metformin, on selected biochemical parameters in male Wistar rats, in an experimental model of diabetes. Forty rats were used for this study. They were divided into eight groups of five rats each, which included: Normal control; Diabetic (D) control; D + N-3; D + low dose Sct (Sct. Lw); D + high dose Sct (Sct. Hi); D + N-3 + Sct.Lw; D + N-3 + Sct.Hi; and D + metformin. Diabetes was induced in overnight fasted rats by the administration of streptozotocin (65 mg/kg b.w., i.p.), 15 min after the administration of nicotinamide (110 mg/kg b.w., i.p.). Nine days later, Sct was administered at 2.5 and 5.0 IU/kg b.w./day (i.m.), while N-3 and metformin were administered at 200 and 180 mg/kg b.w./day (p.o.) respectively, for four weeks. Sct, N-3, and metformin significantly reduced total cholesterol, LDL-C, cortisol, c-telopeptide of type 1 collagen, and collagen type 2 alpha-1. The combined administration of Sct and N-3 had more favorable effects on triglyceride and HDL-C than either monotherapy. Unlike metformin and Sct. Hi, N-3 significantly reduced alkaline phosphatase activity. Moreover, N-3 significantly suppressed the hypocalcaemic, hyperglycaemic, and insulin resistance provoking actions of Sct. Furthermore, N-3 contradicted the hepatic glycogen depletion and inhibition of nitric oxide synthesis brought about by Sct. In conclusion, N-3 demonstrated antagonistic and non-additive actions with Sct. Moreover, the effects of the combined administration of Sct and N-3 were comparable to that of metformin; therefore, they might be considered as therapeutic alternatives in diabetes.