The pathogenesis of post-transplant diabetes mellitus is thought to be partly related to the direct toxic effect of tacrolimus on pancreas and the resultant decrease in insulin synthesis and secretion. This study was performed to evaluate the effect of DPP-IV inhibitor; Sitagliptin (STGL) on pancreatic injury caused by tacrolimus (TAC). Rats were assigned to eight groups: TAC (1 mg/kg/day, s.c.) and STGL (10, 20, 40 mg/kg/day, P.O.) were administered alone and together to the male SD rats for 4 weeks. Body weight (BW) was measured every day. The fasting blood glucose level was measured in each week. The effect of STGL on TAC-induced pancreatic injury was evaluated by intraperitoneal glucose tolerance test (IPGTT). After overnight fasting, blood glucose concentration was measured just before and 30, 60, 90, and 120 min after the dextrose solution (2 g/kg) injection. The area under the curve for glucose (AUCg) was calculated by trapezoidal estimation from the values obtained during the IPGTT. Animals were housed individually in metabolic cages for water and food intake and 24-h urine collection on the day. After four weeks, BW of TAC-treated rats was significantly decreased compared with the VH group or VH+STGL groups. However, concomitant with STGL was increased BW. Water intake was increased in TAC-treated group compared with the VH group, but STGL co-treatment group showed decreased water intake volume. TAC treatment increased blood glucose level (TAC, 279 ± 34 vs. VH, 180 ± 19 mg/dL, P < 0.05) at 1 hours, but STGL co-treatment recovered blood glucose level compared with the TAC-treated group (TAC+STGL10: 258 ± 32; TAC+STGL20: 225 ± 65 vs. TAC: 279 ± 34 mg/dL, P < 0.05). There were significantly different in the AUCg between the VH and STGL (10, 20, 40mg/kg/day) groups in a dose dependant manner. STGL+TAC groups significant decreased the AUCg compared with the TAC alone treated group (TAC+STGL10, 477 ± 32; TAC+STGL20, 441 ± 35 vs. TAC, 511 ± 26 mg/dL.min, P < 0.05). The results of our in vivo study suggest that DPP-IV inhibitor (STGL) has a protective effect on tacrolimus-induced diabetes.

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