APPL1 potentiates insulin secretion in pancreatic β cells by enhancing protein kinase Akt-dependent expression of SNARE proteins in mice.

Proceedings of the National Academy of Sciences of the United States of America
Kenneth K Y ChengAimin Xu

Abstract

Insulin resistance and defective insulin secretion are the two major features of type 2 diabetes. The adapter protein APPL1 is an obligatory molecule in regulating peripheral insulin sensitivity, but its role in insulin secretion remains elusive. Here, we show that APPL1 expression in pancreatic β cells is markedly decreased in several mouse models of obesity and diabetes. APPL1 knockout mice exhibit glucose intolerance and impaired glucose-stimulated insulin secretion (GSIS), whereas transgenic expression of APPL1 prevents high-fat diet (HFD)-induced glucose intolerance partly by enhancing GSIS. In both pancreatic islets and rat β cells, APPL1 deficiency causes a marked reduction in expression of the exocytotic machinery SNARE proteins (syntaxin-1, synaptosomal-associated protein 25, and vesicle-associated membrane protein 2) and an obvious decrease in the number of exocytotic events. Such changes are accompanied by diminished insulin-stimulated Akt activation. Furthermore, the defective GSIS and reduced expression of SNARE proteins in APPL1-deficient β cells can be rescued by adenovirus-mediated expression of APPL1 or constitutively active Akt. These findings demonstrate that APPL1 couples insulin-stimulated Akt activation to...Continue Reading

References

Mar 12, 1998·Nature·D J WithersM F White
Jun 12, 2002·Molecular Biology of the Cell·Thierry CoppolaRomano Regazzi
Aug 24, 2002·Science·Noriko TakahashiHaruo Kasai
Nov 18, 2003·The Journal of Clinical Investigation·Anita M HennigeMorris F White
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
May 16, 2007·The Journal of Cell Biology·Mica Ohara-ImaizumiShinya Nagamatsu
Sep 13, 2007·The Journal of Biological Chemistry·Tsugumichi SaitoPaul F Pilch
Mar 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Natalia GustavssonWeiping Han
May 17, 2008·Annual Review of Nutrition·Ingo B LeibigerPer-Olof Berggren
Jul 14, 2010·Cell Metabolism·Noriko TakahashiHaruo Kasai
Jul 29, 2010·Genesis : the Journal of Genetics and Development·Yinfei TanJoseph R Testa
Jun 3, 2011·The Journal of Clinical Investigation·Susumu SeinoKohtaro Minami

❮ Previous
Next ❯

Citations

May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Weiping Han
Jan 15, 2014·Best Practice & Research. Clinical Endocrinology & Metabolism·Kenneth K Y ChengAimin Xu
Aug 16, 2012·Heart Failure Reviews·Min Park, Gary Sweeney
Apr 2, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Sher Zaman SafiIkram Shah Ismail
Oct 16, 2015·The Journal of Cell Biology·Inna KalaidzidisMarino Zerial
Dec 11, 2013·International Journal of Endocrinology·Kalaivani BatumalaieRajes Qvist
May 22, 2016·Diabetes·Taro YasumaEsteban C Gabazza
Oct 25, 2016·Journal of Diabetes and Its Complications·Michelangela BarbieriMaria Luisa Balestrieri
Jan 22, 2017·Cellular Signalling·Zhuoying LiuFang Hu
Sep 1, 2017·Traffic·Tuanlao WangWanjin Hong
Mar 28, 2018·EMBO Reports·Maria Consolata Miletta, Tamas L Horvath
Oct 30, 2016·The Biochemical Journal·José Antonio Hernández-TrejoPorfirio Nava
Dec 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Jia YuPer-Olof Berggren
Aug 29, 2020·Journal of Personalized Medicine·Dinara E IvanoshchukMikhail I Voevoda
Aug 8, 2013·American Journal of Physiology. Endocrinology and Metabolism·Min ParkGary Sweeney
May 26, 2018·Journal of Cellular Physiology·Hyeon-Jeong HwangPann-Ghill Suh
Sep 14, 2016·The Biochemical Journal·Pia V RöderWeiping Han
Oct 31, 2020·Proceedings of the National Academy of Sciences of the United States of America·Baile WangKenneth K Y Cheng
Dec 10, 2020·Clinical Diabetes and Endocrinology·Ken Munene NkongeTeresa Njeri Nkonge
Mar 7, 2021·International Journal of Molecular Sciences·Diti Chatterjee BhowmickDebbie C Thurmond
Jun 20, 2013·Journal of Cell Science·David A TumbarelloFolma Buss

❮ Previous
Next ❯

Related Concepts

Related Feeds