Beta cell lipotoxicity in the development of type 2 diabetes: the need for species-specific understanding

Patricia Thomas*, Meurig T Gallagher, Gabriela Da Silva Xavier

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

The propensity to develop type 2 diabetes (T2D) is known to have both environmental and hereditary components. In those with a genetic predisposition to T2D, it is widely believed that elevated concentrations of circulatory long-chain fatty acids (LC-FFA) significantly contribute towards the demise of insulin-producing pancreatic β-cells - the fundamental feature of the development of T2D. Over 25 years of research support that LC-FFA are deleterious to β-cells, through a process termed lipotoxicity. However, the work underpinning the theory of β-cell lipotoxicity is mostly based on rodent studies. Doubts have been raised as to whether lipotoxicity also occurs in humans. In this review, we examine the evidence, both in vivo and in vitro, for the pathogenic effects of LC-FFA on β-cell viability and function in humans, highlighting key species differences. In this way, we aim to uncover the role of lipotoxicity in the human pathogenesis of T2D and motivate the need for species-specific understanding.

Original languageEnglish
Article number1275835
JournalFrontiers in Endocrinology
Volume14
DOIs
Publication statusPublished - 8 Dec 2023

Bibliographical note

Copyright © 2023 Thomas, Gallagher and Da Silva Xavier.

Keywords

  • Humans
  • Diabetes Mellitus, Type 2/metabolism
  • Species Specificity
  • Insulin-Secreting Cells/metabolism
  • Insulin/metabolism
  • Fatty Acids/metabolism

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