4.6 Article

MiR-17-5p Inhibits TXNIP/NLRP3 Inflammasome Pathway and Suppresses Pancreatic β-Cell Pyroptosis in Diabetic Mice

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出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.768029

关键词

diabetes mellitus; pancreatic beta-cell; NLRP3 inflammasome; miR-17-5p; pyroptosis

资金

  1. National Natural Science Foundation of China [81873514, 82170357, 81570394]
  2. Guangdong Natural Science Foundation [2021A1515011766, 2017A030311017]

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The study demonstrated that miR-17-5p improves glucose tolerance and pancreatic beta-cell function in diabetic mice, while inhibiting pyroptosis mediated by the TXNIP and NLRP3 inflammasome pathway.
Objective: Diabetes mellitus is a chronic progressive inflammatory metabolic disease with pancreatic beta-cells dysfunction. The present study aimed to investigate whether miR-17-5p plays a protective effect on pancreatic beta-cells function in diabetes mellitus (DM) mice and dissect the underlying mechanism.Methods: C57BL/6J mice were randomly divided into control, DM, DM + Lentivirus negative control (LV-NC), and DM + Lenti-OE (TM) miR-17-5p (LV-miR-17-5) groups. DM was established by feeding a high-fat diet and intraperitoneal injection with streptozotocin (STZ) in mice. Blood glucose and glucose tolerance in circulation were measured. Meanwhile, the activation of nod-like receptor protein 3 (NLRP3) inflammasome, pancreas pyroptosis, and the expression of miR-17-5p and thioredoxin-interacting protein (TXNIP) were detected in the pancreas of DM mice. Pancreatic beta-cell line INS-1 subjected to different concentrations of glucose was used in in vitro experiments.Results: Compared with control mice, glucose tolerance deficit, elevated blood glucose level, and decreased pancreatic islet size, were presented in DM mice, which was associated with a downregulation of miR-17-5p. Importantly, exogenous miR-17-5p alleviated pancreas injury, and consequently improved glucose tolerance and decreased blood glucose in DM mice. In vitro experiments showed that high glucose decreased miR-17-5p expression and impaired insulin secretion in INS-1 cells. Mechanistically, miR-17-5p inhibited the expression of TXNIP and NLRP3 inflammasome activation, and thus decreased pancreatic beta-cell pyroptosis.Conclusion: Our results demonstrated that miR-17-5p improves glucose tolerance, and pancreatic beta-cell function and inhibits TXNIP/NLRP3 inflammasome pathway-related pyroptosis in DM mice.

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