期刊
SCIENTIFIC REPORTS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41598-022-16174-7
关键词
-
资金
- National Institutes of Health [DK084166, DK103197, DK48280, CA246336]
Abnormal miR-30d levels are closely associated with pancreatic beta-cell loss and dysfunction in type 2 diabetes. Overexpression of miR-30d at high levels leads to diet-induced hyperglycemia and beta-cell dysfunction, accompanied by loss of beta-cell identity, increased alpha-cell identity, and excess plasma glucagon levels. Appropriate miR-30d levels are crucial for maintaining normal beta-cell identity and function.
Abnormal microRNA functions are closely associated with pancreatic beta-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 beta-cell functions, we generated two transgenic mouse lines that specifically overexpressed miR-30d in beta-cells at distinct low and high levels. Transgenic overexpressed miR-30d systemically affected beta-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 beta-cell dysfunction. In addition, loss of beta-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 beta-cell-enriched gene expression and induced alpha-cell-enriched gene expression. These findings implicate that an appropriate miR-30d level is essential in maintaining normal beta-cell identity and function.
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