Lysosomes in nutrient signalling: A focus on pancreatic beta-cells

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Meszaros, Gergo | Pasquier, Adrien | Vivot, Kevin | Goginashvili, Alexander | Ricci, Romeo

Edité par CCSD ; Wiley -

Regulated insulin secretion from pancreatic beta-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 beta-cell health under such stresses. Once these mechanisms are overwhelmed, beta-cell failure occurs leading to full-blown Type 2 Diabetes (T2D). Nutrient-dependent macroautophagy represents one such adaptive mechanism in beta-cells. While macroautophagy levels are high and protective in beta-cells in pre-diabetes, they decrease at later stages contributing to beta-cell failure. However, mechanisms compromising macroautophagy in beta-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 beta-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 beta-cell health.

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