Rubicon in pancreatic beta cells plays a limited role in maintaining glucose homeostasis following increased insulin resistance.

Endocrine Journal
Shuhei AoyamaHirotaka Watada

Abstract

Autophagy has been reported to play a crucial role in the maintenance of intracellular homeostasis, including in pancreatic beta cells. Rubicon, which interacts with the phosphoinositide 3-kinase (PI3K) complex, through autophagy-related 14 (ATG14), is among the few autophagy regulators that have been reported to inhibit autophagic flux to date and the deletion of Rubicon has been shown to increase autophagic flux. Based on previous results showing a causal relationship between autophagic dysfunction and pancreatic beta-cell impairment, we hypothesized that the deletion of Rubicon in pancreatic beta cells would improve cell integrity and confer protective effects. To test this hypothesis, we first confirmed that Rubicon knockdown (KD) promoted autophagic flux in βTC3 pancreatic beta-cell line. Next, we generated pancreatic beta-cell-specific Rubicon knockout (βKO) mice, by administering tamoxifen to Rubiconflox/flox:MIP-Cre-ERT mice, which showed normal glucose tolerance and insulin secretion under a normal chow diet, despite successful gene recombination. We also attempted to increase insulin resistance by feeding the mice with a high-fat diet for an additional 2 months to find little differences among the parameters evaluated...Continue Reading

References

Dec 1, 2006·The Journal of Biological Chemistry·Toyoyoshi UchidaHirotaka Watada
Sep 11, 2008·Biochemical and Biophysical Research Communications·Lauge SchäfferJeppe Sturis
Mar 10, 2009·Nature Cell Biology·Kohichi MatsunagaTamotsu Yoshimori
Jan 1, 2013·Diabetes·Etty Bachar-WikstromGil Leibowitz
Jul 19, 2014·The Journal of Clinical Investigation·Jinyoung KimMyung-Shik Lee
Jul 19, 2014·The Journal of Clinical Investigation·Nayumi ShigiharaHirotaka Watada
Jul 19, 2014·The Journal of Clinical Investigation·Jacqueline F RiveraPeter C Butler
Jul 9, 2016·Nature Reviews. Endocrinology·Paul ZimmetPeter H Bennett
Oct 22, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Satoshi TanakaTetsuo Takehara
Nov 8, 2016·Molecular Cell·Takeshi KaizukaNoboru Mizushima
Feb 21, 2019·Nature Communications·Shuhei NakamuraTamotsu Yoshimori
Jun 30, 2019·Biochemical and Biophysical Research Communications·Rieko YazawaHirotaka Watada

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Related Papers

Integrative Physiological and Behavioral Science : the Official Journal of the Pavlovian Society
S Wolf
Medizinische Klinik
G GLOWATZKI
© 2021 Meta ULC. All rights reserved