Effect of metformin and pioglitazone on β-catenin and biochemical markers in sitagliptin-induced pancreatitis in diabetic rats


This study was designed to investigate effect of metformin or pioglitazone on β-catenin and biochemical indicators in sitagliptin-induced pancreatitis. Type 2 diabetes mellitus was induced by high-fat diet/low-dose streptozotocin. Six groups (n = 8) were used: diabetic control group and five treated groups given, for 6 weeks by oral gavage, metformin (100 mg/kg/day), pioglitazone (20 mg/kg/day), sitagliptin (30 mg/kg/day), metformin + sitagliptin (MS), and pioglitazone + sitagliptin (PS). Body weight (BW) and biochemical parameters (fasting blood sugar (FBS), glycated hemoglobin (HbA1c), insulin, total cholesterol (TC), triglycerides (TG), malondialdehyde (MDA), and amylase) were measured. Pancreatic sections were examined using hematoxylin and eosin staining and immunohistochemical staining for β-catenin protein. Only pioglitazone significantly increased BW. All treatments significantly decreased FBS, HbA1c, TC, TG, MDA, and amylase minimally with sitagliptin and maximally with combination therapies. Moreover, all treatments significantly increased insulin except pioglitazone which showed a nonsignificant decrease. Both metformin and pioglitazone ameliorated the diabetic-induced changes while sitagliptin-treated rats showed signs suggestive of pancreatitis. Sitagliptin failed to inhibit the inappropriately increased β-catenin expression predisposing for pancreatitis but helping regenerate streptozotocin-damaged islets. Metformin and pioglitazone alone or combined with sitagliptin decreased the inappropriate β-catenin expression. In conclusion, the decrease in β-catenin seems to be involved in reversal of sitagliptin-associated pancreatitis by metformin or pioglitazone. The better regeneration of islets with metformin and pioglitazone, than sitagliptin, may be due to better effectiveness in controlling diabetes. Sitagliptin should be used in combination with metformin or pioglitazone. Further studies are needed to determine mechanisms underlying role of Wnt/β-catenin in regeneration of islets and exocrine pancreas.

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This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University (KAU), Jeddah, under grant number 195/828/1432. The authors, therefore, acknowledge with thanks DSR technical and financial support.

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Correspondence to Hussam A. S. Murad.

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Murad, H.A.S., Saleh, H.A., Abdulaziz, G.S. et al. Effect of metformin and pioglitazone on β-catenin and biochemical markers in sitagliptin-induced pancreatitis in diabetic rats. Int J Diabetes Dev Ctries 35, 332–339 (2015). https://doi.org/10.1007/s13410-014-0278-8

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  • Metformin
  • Pancreatitis
  • Pioglitazone
  • Sitagliptin
  • Wnt/β-catenin pathway