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Lysosomes in nutrient signalling: A focus on pancreatic β‐cells
Author(s) -
Mészáros Gergő,
Pasquier Adrien,
Vivot Kevin,
Goginashvili Alexander,
Ricci Romeo
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13389
Subject(s) - autophagy , nutrient sensing , microbiology and biotechnology , context (archaeology) , biology , insulin resistance , insulin , secretion , signalling , signal transduction , endocrinology , biochemistry , apoptosis , paleontology
Regulated insulin secretion from pancreatic β‐cells is a major process maintaining glucose homeostasis in mammals. Enhancing insulin release in response to chronic nutrient overload and obesity‐related insulin resistance (pre‐diabetes) requires several adaptive cellular mechanisms maintaining β‐cell health under such stresses. Once these mechanisms are overwhelmed, β‐cell failure occurs leading to full‐blown Type 2 Diabetes (T2D). Nutrient‐dependent macroautophagy represents one such adaptive mechanism in β‐cells. While macroautophagy levels are high and protective in β‐cells in pre‐diabetes, they decrease at later stages contributing to β‐cell failure. However, mechanisms compromising macroautophagy in β‐cells remain poorly understood. In this review, we discuss how recently discovered signalling cascades that emanate from the limiting membrane of lysosomes contribute to changes in macroautophagy flux in physiology and disease. In particular, these mechanisms are put into context with β‐cell function highlighting most recently described links between nutrient‐dependent lysosomal signalling pathways and insulin secretion. Understanding these mechanisms in response to metabolic stress might pave the way for development of more tailored treatment strategies aimed at preserving β‐cell health.