The Impact of Heavy Metals on Pancreatic β-Cell Function: Mechanisms and Implications for Development of Diabetes Mellitus

Le résumé fourni par la source

Environmental exposure to heavy metals is an increasingly recognized risk factor in the development of metabolic disorders, including diabetes mellitus (DM). Pancreatic β-cells are particularly vulnerable to oxidative and functional damage induced by toxicants such as cadmium (Cd), arsenic (As), lead (Pb), and manganese (Mn); however, the mechanisms of toxicity remain inadequately defined. This study aimed to evaluate the cytotoxic, oxidative, and functional effects of CdCl₂, NaAsO₂, MnCl₂, and PbCl₂ on insulin-secreting MIN6 and INS-1 pancreatic β-cell lines. Cells were exposed to different concentrations of heavy metals for 24 h. Cell viability was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, while intracellular reactive oxygen species (ROS) and lipid peroxidation (measured as malondialdehyde, MDA), were quantified to determine oxidative stress. Glucose-stimulated insulin secretion (GSIS) was evaluated using a high glucose challenge and ELISA-based insulin quantification. Exposure to 2 μM CdCl₂ and NaAsO₂, and 5 μM MnCl₂ and PbCl₂, significantly reduced cell viability and insulin secretion in both cell lines. These treatments also induced a marked increase in ROS generation and malondialdehyde (MDA) levels, indicating enhanced oxidative stress and lipid peroxidation. Cd, As, Pb, and Mn exert dose-dependent cytotoxic effects on pancreatic β-cells by impairing viability, disrupting insulin secretion, and inducing oxidative stress. These findings support the hypothesis that chronic exposure to heavy metals contributes to β-cell dysfunction, and may play a role in diabetes pathogenesis. Gaining insight into these mechanisms is essential for guiding environmental health policies and creating targeted intervention strategies.

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