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
Oct 9, 2008·Cell Metabolism·Hye Seung JungMyung-Shik Lee
Oct 9, 2008·Cell Metabolism·Chie EbatoHirotaka Watada
Mar 10, 2009·Nature Cell Biology·Yun ZhongZhenyu Yue
Mar 10, 2009·Nature Cell Biology·Kohichi MatsunagaTamotsu Yoshimori
Aug 31, 2010·Diabetes·Barton WicksteedPeter J Dempsey
Jan 1, 2013·Diabetes·Etty Bachar-WikstromGil Leibowitz
Jul 25, 2013·Diabetes·Adam D BarlowTerry P Herbert
May 9, 2014·Diabetes Care·Philippe A HalbanGordon C Weir
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 24, 2014·BMC Genomics·Christopher BennerMark O Huising
Jun 23, 2015·Nature Cell Biology·Jennifer MartinezDouglas R Green
Jan 23, 2016·Autophagy·Daniel J KlionskySusu M Zughaier
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