In pancreatic beta cell, excessive and prolonged increase of glucose causes beta cell dysfunction which is characterized by impaired insulin synthesis and secretion, termed the glucotoxicity. Although it is known that both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, other molecular mechanisms that protect from glucotoxicity are poorly defined. We investigated the effect of Lin28a overexpression on glucotoxicity-induced beta cell dysfunction. In this study, we found that high glucose leads to a decrease in Lin28a mRNA and protein expression, followed by a decrease in insulin gene expression and secretion in the rat insulinoma cell line, INS-1. In addition, PDX-1and BETA2 mRNA and protein expression were downregulated by high glucose in INS-1. Similarly, mRNA expression of Lin28a and insulin was decreased in pancreas of high fat diet induced diabetic mouse. Adenovirus mediated Lin28a overexpression in INS-1 reversed the glucotoxicity-induced downregulation of insulin, PDX-1 and BETA2 expression, and improved glucose stimulated insulin secretion (GSIS). In mouse islet, mRNA expressions of insulin, PDX-1 and ki67 and GSIS were decreased by glucotoxicity. Lin 28a overexpression in mouse islet partially restored their expression and GSIS. These results suggest that Lin28a protects pancreatic beta cells from glucotoxicity through regulation of insulin transcription factors.


K. Lee: None. Y. Hwang: None. J. Choi: None.


Daegu Gyeongbuk Institute of Science and Technology (18-LC-01, 2018010133)

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