Zooming in on Diabetes Journal Club February 25, 2021
Zooming in on Diabetes Thursday, February 25 at 9:00 am (PST)
Presenter: Dr. Shogo Ida, Post-Doctoral Fellow, Kieffer Lab, Life Sciences Institute, UBC Vancouver
Title of Paper: Glucagon Resistance and Decreased Susceptibility to Diabetes in a Model of Chronic Hyperglucagonemia
Abstract: Elevation of glucagon levels and increase in a-cell mass are associated with states of hyperglycemia in diabetes. Our previous studies have highlighted the role of nutrient signaling via mTOR complex 1 (mTORC1) regulation that controls glucagon secretion and a-cell mass. In the current studies we investigated the effects of activation of nutrient signaling by conditional deletion of the mTORC1 inhibitor, TSC2, in a-cells (aTSC2KO). We showed that activation of mTORC1 signaling is sufficient to induce chronic hyperglucagonemia as a result of a-cell proliferation, cell size, and mass expansion. Hyperglucagonemia in aTSC2KO was associated with an increase in glucagon content and enhanced glucagon secretion. This model allowed us to identify the effects of chronic hyperglucagonemia on glucose homeostasis by inducing insulin secretion and resistance to glucagon in the liver. Liver glucagon resistance in aTSC2KO mice was characterized by reduced expression of the glucagon receptor (GCGR), PEPCK, and genes involved in amino acid metabolism and urea production. Glucagon resistance in aTSC2KO mice was associated with improved glucose levels in streptozotocin-induced b-cell destruction and high-fat diet–induced glucose intolerance. These studies demonstrate that chronic hyperglucagonemia can improve glucose homeostasis by inducing glucagon resistance in the liver.
PMID: 33239450
URL link to publication source: https://diabetes.diabetesjournals.org/content/70/2/477
“Zooming in on Diabetes” is a virtual journal club and was launched in March 2020.
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.
