2. Academic Validation
  3. MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake

MicroRNA-21 promotes pancreatic β cell function through modulating glucose uptake

  • Nat Commun. 2022 Jun 21;13(1):3545. doi: 10.1038/s41467-022-31317-0.
Ruiling Liu  # 1 2,  Cuilian Liu  # 3,  Xiaozhen He 2,  Peng Sun 4,  Bin Zhang 2,  Haoran Yang 3,  Weiyun Shi 5,  Qingguo Ruan 6 7
Affiliations

Affiliations

  • 1 School of Basic Medicine, Qingdao University, 266071, Qingdao, People's Republic of China.
  • 2 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 266071, Qingdao, People's Republic of China.
  • 3 Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, People's Republic of China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, 266000, Qingdao, People's Republic of China.
  • 5 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 266071, Qingdao, People's Republic of China. weiyunshi@163.com.
  • 6 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, 266071, Qingdao, People's Republic of China. ruanqg222@hotmail.com.
  • 7 Center for Protein and Cell-Based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, People's Republic of China. ruanqg222@hotmail.com.
  • # Contributed equally.
PMID: 35729232 DOI: 10.1038/s41467-022-31317-0
Abstract

Pancreatic β cell dysfunction contributes to the pathogenesis of type 2 diabetes. MiR-21 has been shown to be induced in the islets of glucose intolerant patients and type 2 diabetic mice. However, the role of miR-21 in the regulation of pancreatic β cell function remains largely elusive. In the current study, we identify the pathway by which miR-21 regulates glucose-stimulated Insulin secretion utilizing mice lacking miR-21 in their β cells (miR-21βKO). We find that miR-21βKO mice develop glucose intolerance due to impaired glucose-stimulated Insulin secretion. Mechanistic studies reveal that miR-21 enhances glucose uptake and subsequently promotes Insulin secretion by up-regulating GLUT2 expression in a miR-21-Pdcd4-AP-1 dependent pathway. Over-expression of GLUT2 in knockout islets results in rescue of the impaired glucose-stimulated Insulin secretion. Furthermore, we demonstrate that delivery of miR-21 into the pancreas of type 2 diabetic db/db male mice is able to promote GLUT2 expression and reduce blood glucose level. Taking together, our results reveal that miR-21 in islet β cell promotes Insulin secretion and support a role for miR-21 in the regulation of pancreatic β cell function in type 2 diabetes.

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