Acarbose ameliorates spontaneous type-2 diabetes in db/db mice by inhibiting PDX-1 methylation

Pancreatic and duodenal homeobox (PDX)-1 is a gene that plays an important role in pancreatic development and function. Type-2 diabetes mellitus (T2DM) is a metabolic disease associated with insulin resistance and impaired islet β-cell function. There is evidence that methylation of PDX-1 plays a role in the development of T2DM. Acarbose is an α-glucosidase inhibitor that can effectively delay the absorption of glucose by the body. The aim of the present study was to examine the effect of acarbose on PDX-1 methylation in islet β-cells in spontaneous type-2 diabetic db/db mice. The effect of acarbose on glucose and lipid metabolism in these mice was assessed by measuring food intake, body weight, glycated hemoglobin (HbA1c), glucagon, serum total cholesterol and triglyceride levels, and fasting blood glucose (FBG). Blood glucose levels were also analyzed using intraperitoneal glucose tolerance and insulin tolerance tests. Immunohistochemistry was used to evaluate the effect of acarbose on pathological changes in the pancreas. Moreover, a BrdU assay was used to analyze cell proliferation. Lastly, the effect of acarbose on PDX-1 methylation was evaluated in mice using methylation-specific PCR and western blot analysis. In the present study, body weight significantly increased in the acarbose group, compared to the normal group. The levels of HbA1c and glucagon in the T2DM group significantly increased, compared with the normal group, but significantly decreased in acarbose-treated mice. Moreover, FBG levels significantly decreased in the acarbose groups compared with T2DM mice. Acarbose also promoted cell proliferation, compared with untreated T2DM mice. In addition, PDX-1 methylation and cytoplasmic expression levels were both downregulated in the acarbose group, compared with the T2DM group. In conclusion, these results suggested that acarbose could promote the proliferation of islet β-cells and inhibit PDX-1 methylation in islet β cells from diabetic mice. Thus, acarbose may provide a new strategy to treat T2DM.