Abstract
Although both insulin and glucagon are intimately involved in the regulation of glucose homeostasis, the intrinsic control of glucagon secretion, including the biogenesis and exocytosis of glucagon-containing granules, is far less understood compared with that of insulin. As Brefeldin A-inhibited guanine nucleotide exchange protein 3 (BIG3) is a negative regulator of insulin-granule biogenesis and insulin secretion, we investigated whether BIG3 plays any role in alpha-cells and glucagon secretion. We examined the expression of BIG3 in islet cells by immuno-fluorescence and confocal microscopy, and measured glucagon production and secretion in BIG3-depleted and wild-type mice, islets and cells. BIG3 is highly expressed in pancreatic alpha-cells in addition to beta-cells, but is absent in delta-cells. Depletion of BIG3 in alpha-cells leads to elevated glucagon production and secretion. Consistently, BIG3-knockout (BKO) mice display increased glucagon release under hypoglycemic conditions. Together with our previous studies, the current data reveal a conserved role for BIG3 in regulating alpha- and beta-cell functions. We propose that BIG3 negatively regulates hormone production at the secretory granule biogenesis stage and that s...Continue Reading
References
May 27, 1993·Nature·C AmmäläP Rorsman
Jul 3, 2002·Nature Reviews. Genetics·Helena Edlund
Feb 18, 2004·The Journal of Physiology·Sven GöpelPatrik Rorsman
Jan 31, 2007·Endocrine Reviews·Jesper GromadaClaes B Wollheim
Apr 6, 2007·Endocrine Reviews·Beth Elaine Dunning, John E Gerich
Sep 20, 2007·Endocrine Reviews·Yuk M LeungHerbert Y Gaisano
Mar 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Natalia GustavssonWeiping Han
Jun 5, 2008·Cell Metabolism·Herbert Y Gaisano, Yuk M Leung
Jan 28, 2009·The Journal of Physiology·Natalia GustavssonWeiping Han
Mar 20, 2009·Journal of Cell Science·Zhanxiang Wang, Debbie C Thurmond
Jun 9, 2009·Bioscience Reports·Natalia Gustavsson, Weiping Han
Jul 24, 2010·PloS One·Phing-How LouWeiping Han
Oct 28, 2010·Diabetologia·N GustavssonW Han
Jan 21, 2011·Physiological Reviews·Tom L van BelleMatthias G von Herrath
Jan 29, 2011·Diabetes·Young LeeRoger H Unger
Feb 3, 2011·American Journal of Physiology. Endocrinology and Metabolism·Juris J MeierStephan Schneider
Jun 7, 2011·Pflügers Archiv : European journal of physiology·Sofia A AnderssonLena Eliasson
Jul 22, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tao LiuZhuan Zhou
Sep 20, 2011·Diabetes·Fabrizio ThorelPedro L Herrera
Dec 25, 2012·Trends in Endocrinology and Metabolism : TEM·Joel F Habener, Violeta Stanojevic
Aug 6, 2013·Annual Review of Cell and Developmental Biology·Hung Ping ShihMaike Sander
Sep 18, 2013·Nature Reviews. Endocrinology·Frances M Ashcroft, Patrik Rorsman
Oct 1, 2013·Diabetologia·Xiaorui WangWeiping Han
Apr 9, 2014·EMBO Reports·Hongyu LiWeiping Han
Apr 22, 2014·Trends in Endocrinology and Metabolism : TEM·Herbert Y Gaisano
Jun 20, 2014·Preventing Chronic Disease·Carla L DeSistoAndrea J Sharma
Aug 21, 2014·American Journal of Physiology. Endocrinology and Metabolism·Tao LiuWeiping Han
Citations
Oct 30, 2016·Journal of Neurochemistry·Tao LiuWeiping Han
Nov 9, 2017·Molecular & Cellular Proteomics : MCP·Taewook KangMartin R Larsen
Feb 5, 2019·Frontiers in Endocrinology·Farzad Asadi, Savita Dhanvantari
Dec 21, 2021·Islets·Farzad Asadi, Savita Dhanvantari