Emodin Alleviates High-Glucose-Induced Pancreatic β-Cell Pyroptosis by Inhibiting NLRP3/GSDMD Signaling.

Yiqian Xing,Chunguang Xie,Jian Kang,Ya Liu,Xiyu Zhang,Yuchi He,Yuan Zhang,Sihan Peng,Heting Wang,Fernanda Tonelli

doi:10.1155/2022/5276832

Abstract

Diabetes mellitus (DM) is a chronic noninfectious disease that is mainly featured by pancreatic β-cell (β-cell) dysfunction and impaired glucose homeostasis. Currently, the pathogenesis of dysfunction of the β-cells in DM remains unclear, and therapeutic approaches to it are limited. Emodin (EMD), a natural anthraquinone derivative, has been preliminarily proven to show antidiabetic effects. However, the underlying mechanism of EMD on β-cells still needs to be elucidated. In this study, we investigated the protective effects of EMD on the high glucose (50 mM)-induced INS-1 cell line and the underlying mechanism. INS-1 cells were treated with EMD (5, 10, and 20 μM) when exposed to high glucose. The effects of EMD were examined by using the inverted phase-contrast microscope, qRT-PCR, ELISA, and western blot. The results showed that EMD could alleviate cellular morphological changes, suppress IL-1β and LDH release, and promote insulin secretion in high-glucose-induced INS-1 cells. Furthermore, EMD inhibits NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage to alleviate pyroptosis induced by high glucose. Overexpression of NLRP3 reversed the above changes caused by EMD. Collectively, our findings suggest that EMD attenuates high-glucose-induced β-cell pyroptosis by inhibiting NLRP3/GSDMD signaling.

Highlights

Diabetes mellitus (DM), a severe disease with epidemic spreading throughout the world, is characterized by hyperglycemia
Driven by the lack of insulin or ineffective production of insulin in the pancreas, high blood sugar gives rise to many life-threatening diabetic complications and makes DM a leading cause of cardiovascular morbidity and mortality, renal failure, amputations, and blindness [2]. β-Cells are pivotal for the maintenance of blood glucose homeostasis
INS-1 cells were seeded in 6-well plates when 90% confluence. en, cells were randomly divided into 5 groups, respectively, with the following interventions: (1) normal control (NC) group; (2) high glucose (HG) group; (3, 4, 5) HG + EMD (5, 10, and 20 μM) groups

Summary

Introduction

Diabetes mellitus (DM), a severe disease with epidemic spreading throughout the world, is characterized by hyperglycemia. As of 2019, the number of people with DM has reached a total of 463 million. It is estimated that the number will reach 578 million by the year of 2030 and 700 million by 2045 [1]. Β-Cells are pivotal for the maintenance of blood glucose homeostasis. Driven by the lack of insulin or ineffective production of insulin in the pancreas, high blood sugar gives rise to many life-threatening diabetic complications and makes DM a leading cause of cardiovascular morbidity and mortality, renal failure, amputations, and blindness [2]. They are the only source of insulin in humans; they are a prime target in DM. Many synthetic drugs have been developed to decrease hyperglycemia and preserve β-cell function, but still, a complete cure is not provided by any of the molecules. Continuous use of some synthetic agents may cause adverse side effects

Methods

Results

Conclusion