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 β-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 β-cell survival and prevented HFD-induced β-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 β-cells. Conclusions Blueberry-supplemented diet can prevent obesity-induced insulin resistance by improving insulin sensitivity and protecting pancreatic β-cells. Blueberry supplementation has the potential to protect and improve health conditions for both type 1 and type 2 diabetes patients. Electronic supplementary material The online version of this article (10.1186/s12986-019-0363-6) contains supplementary material, which is available to authorized users.
Pancreatic β-cell dysfunction is central to the development and progression of type 2 diabetes. Dysregulation of miRNAs has been associated with pancreatic islet dysfunction in type 2 diabetes. Previous study has shown that miR-483 is expressed relatively higher in β-cells than in α-cells. To explore the physiological function of miR-483, we generated a beta-cell specific knockout mouse model of miR-483. Loss of miR-483 enhances high-fat diet-induced hyperglycemia and glucose intolerance by the attenuation of diet-induced insulin release. Intriguingly, mice with miR-483 deletion exhibited loss of β-cell features, as indicated by elevated expression of aldehyde dehydrogenase family 1, subfamily A3 (Aldh1a3), a marker of beta-cell dedifferentiation. Moreover, Aldh1a3 was validated as a direct target of miR-483 and overexpression of miR-483 repressed Aldh1a3 expression. Genetic ablation of miR-483 also induced alterations in blood lipid profile. Collectively, these data suggest that miR-483 is critical in protecting β-cell function by repressing β-cell disallowed gene Aldh1a3. The dysregulated miR-483 may impair insulin secretion and initiate β-cell dedifferentiation during the development of type 2 diabetes.
Abnormal microRNA functions are closely associated with pancreatic β-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 β-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in β-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected β-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 β-cell dysfunction. In addition, loss of β-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 β-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 β-cell identity and function.
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