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. 2023 Dec 8;14:1275835. doi: 10.3389/fendo.2023.1275835

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Copyright © 2023 Thomas, Gallagher and Da Silva Xavier

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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The current theory of β-cell lipotoxicity during the progression of T2D. A sedentary lifestyle coupled with a high-calorie diet leads to an accumulation of adipose tissue with hyperinsulinemia and elevated FFA, contributing towards insulin resistance of the peripheral tissue and hyperglycaemia. In genetically susceptible subjects, increased circulatory FFA concentrations are believed to contribute towards the death and dysfunction of insulin-producing pancreatic β-cells (lipotoxicity), leading to overt T2D.