Publication

Palmitate impairs autophagic degradation via oxidative stress-perilysosomal Ca2+ overload-mTORC1 activation in pancreatic β-cells

2025

Abstract

Saturated fatty acids impose lipotoxic stress on pancreatic β-cells, leading to β-cell failure and diabetes. In this study, we investigate the critical role of organellar Ca 2+ disturbance on defective autophagy and β-cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca 2+ elevation, sustained mTORC1 activation on the lysosomal membrane, suppression of the lysosomal transient receptor potential mucolipin 1 (TRPML1) channel, and accumulation of undigested autophagosomes in β-cells. These Ca 2+ aberrations with autophagy defects by palmitate were prevented by an mTORC1 inhibitor or a mitochondrial superoxide scavenger. To alleviate perilysosomal Ca 2+ overload, strategies such as lowering extracellular Ca 2+ , employing

Official source

https://infoscience.epfl.ch/entities/publication/5771ca86-7682-42bd-9ec4-a136d7181007

About this result

This page is automatically generated and may contain information that is not correct, complete, up-to-date, or relevant to your search query. The same applies to every other page on this website. Please make sure to verify the information with EPFL's official sources.

Graph Chat

Chat with Graph Search

Ask any question about EPFL courses, lectures, exercises, research, news, etc. or try the example questions below.

DISCLAIMER: The Graph Chatbot is not programmed to provide explicit or categorical answers to your questions. Rather, it transforms your questions into API requests that are distributed across the various IT services officially administered by EPFL. Its purpose is solely to collect and recommend relevant references to content that you can explore to help you answer your questions.

2025

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/5771ca86-7682-42bd-9ec4-a136d7181007

About this result

Related concepts (24)

Fatty acid

In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, from 4 to 28. Fatty acids are a major component of the lipids (up to 70% by weight) in some species such as microalgae but in some other organisms are not found in their standalone form, but instead exist as three main classes of esters: triglycerides, phospholipids, and cholesteryl esters.

Beta cell

Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are diminished, leading to insufficient insulin secretion and hyperglycemia. The primary function of a beta cell is to produce and release insulin and amylin. Both are hormones which reduce blood glucose levels by different mechanisms.

Saturated fat

A saturated fat is a type of fat in which the fatty acid chains have all single bonds. A fat known as a glyceride is made of two kinds of smaller molecules: a short glycerol backbone and fatty acids that each contain a long linear or branched chain of carbon (C) atoms. Along the chain, some carbon atoms are linked by single bonds (-C-C-) and others are linked by double bonds (-C=C-). A double bond along the carbon chain can react with a pair of hydrogen atoms to change into a single -C-C- bond, with each H atom now bonded to one of the two C atoms.

Related publications (1)

Palmitate impairs autophagic degradation via oxidative stress-perilysosomal Ca2+ overload-mTORC1 activation in pancreatic β-cells

Chat with Graph Search

LRH-1-dependent glucose sensing determines intermediary metabolism in liver