AUTHOR=Liu Sijun , Tang Ge , Duan Fengqi , Zeng Cheng , Gong Jianfeng , Chen Yanming , Tan Hongmei 

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

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.768029

DOI=10.3389/fcvm.2021.768029

ISSN=2297-055X

ABSTRACT=Objective: Diabetes mellitus (DM) is a chronic progressive inflammatory metabolic disease with pancreatic β-cells dysfunction. The present study aimed to investigate whether miR-17-5p plays protective effect on pancreatic β-cells function in 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™ miR-17-5p (LV-miR-17-5) groups. DM was established by feeding 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 pancreas of DM mice. Pancreatic β-cell line INS-1 subjected to different concentration 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 β-cell pyroptosis. 
Conclusion: Our results demonstrate that miR-17-5p improves the glucose tolerance, and pancreatic β-cell function and inhibits TXNIP/NLRP3 inflammasome pathway-related pyroptosis in DM mice.