Short-term inhibition of autophagy benefits pancreatic β-cells by augmenting ether lipids and peroxisomal function, and by countering depletion of n-3 polyunsaturated fatty acids after fat-feeding.

ABSTRACT:

Objective

Investigations of autophagy in β-cells have usually focused on its homeostatic function. More dynamic roles in inhibiting glucose-stimulated insulin secretion (GSIS), potentially involving remodelling of cellular lipids, have been suggested from in vitro studies but not evaluated in vivo.

Methods

We employed temporally-regulated deletion of the essential autophagy gene, Atg7, in β-cells. Mice were fed chow or high-fat diets (HFD), in conjunction with deletion of Atg7 for the last 3 weeks (short-term model) or 9 weeks (long-term model). Standard in vivo metabolic phenotyping was undertaken, and 450 lipid species in islets quantified ex vivo using mass spectroscopy (MS). MIN6 cells were also employed for lipidomics and secretory interventions.

Results

β-cell f

SUBMITTER: Chu KY 

PROVIDER: S-EPMC7322075 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature