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

Area of Science:

• Endocrinology
• Cell Biology
• Pharmacology

Background:

• Diabetes mellitus (DM) involves pancreatic beta-cell dysfunction and impaired glucose homeostasis.
• The precise mechanisms driving beta-cell dysfunction in DM are not fully understood, limiting therapeutic options.
• Emodin (EMD), a natural compound, shows preliminary antidiabetic effects, but its mechanism on beta-cells requires elucidation.

Purpose of the Study:

• To investigate the protective effects of Emodin (EMD) on high glucose-induced pancreatic beta-cell dysfunction.
• To elucidate the underlying molecular mechanisms of EMD's action on beta-cells, specifically focusing on pyroptosis.

Main Methods:

• INS-1 cells were exposed to high glucose (50 mM) and treated with varying concentrations of EMD (5, 10, 20 μM).
• Cellular changes were assessed using microscopy, qRT-PCR, ELISA, and Western blot.
• Key pathways investigated included NOD-like receptor protein 3 (NLRP3) activation and gasdermin D (GSDMD) cleavage.

Main Results:

• EMD treatment alleviated morphological damage, reduced IL-1β and LDH release, and enhanced insulin secretion in high glucose conditions.
• EMD significantly inhibited high glucose-induced pyroptosis by suppressing NLRP3 activation and GSDMD cleavage.
• Overexpression of NLRP3 counteracted the protective effects of EMD, confirming the pathway's involvement.

Conclusions:

• Emodin (EMD) demonstrates significant protective effects against high glucose-induced pancreatic beta-cell pyroptosis.
• The mechanism involves the inhibition of the NLRP3/GSDMD signaling pathway.
• EMD represents a promising therapeutic agent for managing beta-cell dysfunction in diabetes mellitus.