Transgenic overexpression of microRNA-30d in pancreatic beta-cells progressively regulates beta-cell function and identity.

Abnormal microRNA functions are closely associated with pancreatic ß-cell loss and dysfunction in type 2 diabetes. Dysregulation of miR-30d has been reported in the individuals with diabetes. To study how miR-30d affects pancreatic ß-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in ß-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected ß-cell function. Elevated miR-30d at low-level (TgL, 2-fold) had mild effects on signaling pathways and displayed no significant changes to metabolic homeostasis. In contrast, transgenic mice with high-level of miR-30d expression (TgH, 12-fold) exhibited significant diet-induced hyperglycemia and ß-cell dysfunction. In addition, loss of ß-cell identity was invariably accompanied with increased insulin/glucagon-double positive bihormonal cells and excess plasma glucagon levels. The transcriptomic analysis revealed that miR-30d overexpression inhibited ß-cell-enriched gene expression and induced α-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal ß-cell identity and function.

Whole blueberry protects pancreatic beta-cells in diet-induced obese mouse.

BACKGROUND: Blueberry is rich in bioactive substances and possesses powerful antioxidant potential, which can protect against oxidant-induced and inflammatory cell damage and cytotoxicity. The aim of this study was to determine how blueberry affects glucose metabolism and pancreatic ß-cell proliferation in high fat diet (HFD)-induced obese mice. METHODS: Wild type male mice at age of 4 weeks received two different kinds of diets: high-fat diet (HFD) containing 60% fat or modified HFD supplemented with 4% (wt:wt) freeze-dried whole blueberry powder (HFD + B) for 14 weeks. A separate experiment was performed in mice fed with low-fat diet (LFD) containing 10% fat or modified LFD + B supplemented with 4% (wt:wt) freeze-dried whole blueberry powder. The metabolic parameters including blood glucose and insulin levels, glucose and insulin tolerances were measured. RESULTS: Blueberry-supplemented diet significantly increased insulin sensitivity and glucose tolerance in HFD + B mice compared to HFD mice. However, no difference was observed in blood glucose and insulin sensitivity between LFD + B and LFD mice. In addition, blueberry increased ß-cell survival and prevented HFD-induced ß-cell expansion. The most important finding was the observation of presence of small scattered islets in blueberry treated obese mice, which may reflect a potential role of blueberry in regenerating pancreatic ß-cells. CONCLUSIONS: Blueberry-supplemented diet can prevent obesity-induced insulin resistance by improving insulin sensitivity and protecting pancreatic ß-cells. Blueberry supplementation has the potential to protect and improve health conditions for both type 1 and type 2 diabetes patients.