Zooming in on Diabetes Journal Club March 2
Zooming in on Diabetes
Thursday, March 2, at 09:00
Dr. Jelena Kolic, Research Associate, Johnson Lab, Life Sciences Institute, University of British Columbia (Vancouver)
Presentation Information
Title of Paper:
Palmitoylation couples insulin hypersecretion with beta cell failure in diabetes
Abstract:
Hyperinsulinemia often precedes type 2 diabetes. Palmitoylation, implicated in exocytosis, is reversed by acyl-protein thioesterase 1 (APT1). APT1 biology was altered in pancreatic islets from humans with type 2 diabetes, and APT1 knockdown in nondiabetic islets caused insulin hypersecretion. APT1 knockout mice had islet autonomous increased glucose-stimulated insulin secretion that was associated with prolonged insulin granule fusion. Using palmitoylation proteomics, we identified Scamp1 as an APT1 substrate that localized to insulin secretory granules. Scamp1 knockdown caused insulin hypersecretion. Expression of a mutated Scamp1 incapable of being palmitoylated in APT1-deficient cells rescued insulin hypersecretion and nutrient-induced apoptosis. High-fat-fed islet-specific APT1-knockout mice and global APT1-deficient db/db mice showed increased b cell failure. These findings suggest that APT1 is regulated in human islets and that APT1 deficiency causes insulin hypersecretion leading to b cell failure, modeling the evolution of some forms of human type 2 diabetes.
PMID:
36634673
URL link to publication source:
https://pubmed.ncbi.nlm.nih.gov/36634673/
It is a joint initiative across the University of British Columbia campuses including the Life Sciences Centre and the BC Children’s Hospital.
This Journal Club is designed for trainees to develop skills in critical evaluation of recent articles in the scientific literature related to diabetes research.
The intended audience are academic research trainees and faculty involved in diabetes research in British Columbia, Canada.
The journal club is held on Tuesdays and Thursdays via ZOOM.
