Lipotoxicity in the Pancreatic Beta Cell: Not Just Survival and Function, but Proliferation as Well?
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Abstract
Free fatty acids (FFAs) exert both positive and negative effects on beta cell survival and insulin secretory function, depending on concentration, duration, and glucose abundance. Lipid signals are mediated not only through metabolic pathways, but also through cell surface and nuclear receptors. Toxicity is modulated by positive signals arising from circulating factors such as hormones, growth factors and incretins, as well as negative signals such as inflammatory mediators and cytokines. Intracellular mechanisms of lipotoxicity include metabolic interference and cellular stress responses such as oxidative stress, endoplasmic reticulum (ER) stress, and possibly autophagy. New findings strengthen an old hypothesis that lipids may also impair compensatory beta cell proliferation. Clinical observations continue to support a role for lipid biology in the risk and progression of both type 1 (T1D) and type 2 diabetes (T2D). This review summarizes recent work in this important, rapidly evolving field.
Keywords
Pancreatic beta cell Islet Lipotoxicity Glucolipotoxicity Lipid Triglyceride Free fatty acid Nonesterified fatty acid Growth factors Inflammation Metabolism gpr40 FFAR1 Fatty acid receptor Oxidative stress Endoplasmic reticulum stress Autophagy PPAR Cell cycle Proliferation Insulin secretion ApoptosisNotes
Acknowledgments
Funding supporting this work includes NIH: DK095140 (LCA).
Compliance with Ethics Guidelines
ᅟ
Conflict of Interest
Rohit B. Sharma and Laura C. Alonso declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References
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