Inhibition of Foxo1 mediates protective effects of ghrelin against lipotoxicity in MIN6 pancreatic beta-cells

Peptides
Wei WangGuoliang Liu

Abstract

Ghrelin is a 28-amino-acid peptide secreted predominantly by X/A-like cells of the gastric fundus. Ghrelin increases pancreatic beta-cell proliferation and survival via sequential activation of phosphatidylinositol-3 kinase (PI3K) and Akt. The transcription regulator Foxo1 is a prominent effector of PI3K/Akt; when it is inhibited, pancreatic beta-cells are protected against fatty-acid-induced apoptosis. We investigated the role of Foxo1 in the protective effect of ghrelin under lipotoxic conditions in the MIN6 pancreatic beta-cell line. Results showed that ghrelin promoted cell proliferation and attenuated palmitate-induced apoptosis in cultured MIN6 cells. Nuclear exclusion of Foxo1 was necessary for the function of ghrelin. Treatment of MIN6 cells with palmitate and ghrelin-induced rapid nuclear exclusion and phosphorylation of Foxo1. Unlike the JNK inhibitor SP600125, Akt inhibitor IV blocked the anti-lipotoxic effect of ghrelin and stimulated Foxo1 nuclear translocation. In addition, treatment with ghrelin combined with SP600125 showed a synergistic antiapoptotic effect in palmitate-treated MIN6 cells. Ghrelin also inhibited the endoplasmic reticulum stress pathway of apoptosis in MIN6 cells, decreased expression of cytopla...Continue Reading

References

Jan 12, 2001·Molecular and Cellular Biology·A H KimM V Chao
Nov 29, 2001·The Journal of Biological Chemistry·Masahiro MurataKazuo Chihara
Jul 26, 2002·Archives of Biochemistry and Biophysics·Karen C Arden, William H Biggs
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Oct 24, 2002·The Journal of Biological Chemistry·Christian E WredeChristopher J Rhodes
Jan 18, 2003·Developmental Cell·Jun NakaeDomenico Accili
May 29, 2003·The Journal of Biological Chemistry·Cynthia L KelpeVincent Poitout
Sep 3, 2003·Biochemical and Biophysical Research Communications·Mark S DuxburyEdward E Whang
Dec 20, 2003·Cell Death and Differentiation·S Oyadomari, M Mori
Apr 20, 2004·Diabetologia·J ButeauM Prentki
Jun 5, 2004·Molecular Endocrinology·Min Seon KimKyong Soo Park
Jan 12, 2005·The Journal of Endocrinology·Giuseppina MaccarinelliDaniela Cocchi
Feb 5, 2005·The Journal of Biological Chemistry·Claire C BastieNada A Abumrad
Aug 11, 2005·Journal of Cell Science·Haiyan WangClaes B Wollheim
Feb 3, 2006·Journal of Neuroendocrinology·J P Camiña
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
May 19, 2007·Endocrine Journal·Tadahiro Kitamura, Yukari Ido Kitamura
Jul 3, 2007·Cell·Brendan D Manning, Lewis C Cantley
Aug 28, 2007·Biochemical and Biophysical Research Communications·Hong ZhaoZhongQiu Xin
Dec 1, 2007·Endocrine Reviews·Décio L EizirikMiriam Cnop
Apr 9, 2008·Peptides·João-Bruno Soares, Adelino F Leite-Moreira

❮ Previous
Next ❯

Citations

Jan 26, 2013·DNA and Cell Biology·Shiying ShaoXuefeng Yu
Mar 26, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ricardo LageMiguel López
Sep 4, 2015·Apoptosis : an International Journal on Programmed Cell Death·Feng HaoXuejun Li
Sep 20, 2018·Diabetes, Obesity & Metabolism·Tiziana NapolitanoPatrick Collombat
May 1, 2021·International Journal of Molecular Sciences·Jan ŠrámekJan Kovář
Dec 24, 2010·Current Opinion in Endocrinology, Diabetes, and Obesity

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.