Lipopolysaccharides impair insulin gene expression in isolated islets of Langerhans via Toll-Like Receptor-4 and NF-κB signalling.

PloS One
Julie AmyotVincent Poitout

Abstract

Type 2 diabetes is characterized by pancreatic β-cell dysfunction and is associated with low-grade inflammation. Recent observations suggest that the signalling cascade activated by lipopolysaccharides (LPS) binding to Toll-Like Receptor 4 (TLR4) exerts deleterious effects on pancreatic β-cell function; however, the molecular mechanisms of these effects are incompletely understood. In this study, we tested the hypothesis that LPS alters insulin gene expression via TLR4 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in islets. A 24-h exposure of isolated human, rat and mouse islets of Langerhans to LPS dose-dependently reduced insulin gene expression. This was associated in mouse and rat islets with decreased mRNA expression of pancreas-duodenum homebox-1 (PDX-1) and mammalian homologue of avian MafA/l-Maf (MafA). Accordingly, LPS exposure also decreased glucose-induced insulin secretion. LPS repression of insulin, PDX-1 and MafA expression, as well as its inhibition of insulin secretion, were not observed in islets from TLR4-deficient mice. LPS inhibition of β-cell gene expression in rat islets was prevented by inhibition of the NF-κB pathway, but not the p38 mitogen-activated protein kinase (p38 MAP...Continue Reading

References

Jan 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·K Docherty, A R Clark
Apr 10, 1997·The New England Journal of Medicine·P J Barnes, M Karin
Dec 8, 1998·The Journal of Experimental Medicine·C J KirschningM Rothe
Nov 24, 1999·The Journal of Biological Chemistry·E LienD T Golenbock
Sep 18, 2002·The Journal of Clinical Investigation·Kathrin MaedlerMarc Y Donath
May 29, 2003·The Journal of Biological Chemistry·Cynthia L KelpeVincent Poitout
Dec 31, 2003·Nutrition·Paska A PermanaP Antonio Tataranni
Sep 11, 2004·Biochemical and Biophysical Research Communications·Bin He, Georg F Weber
Jan 25, 2005·The Journal of Biological Chemistry·Li ZhaoRoland Stein
May 3, 2005·Diabetologia·H Kolb, T Mandrup-Poulsen
Mar 22, 2006·The Journal of Nutrition·Vincent PoitoutJamie S Harmon
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andreas ZwergalKorbinian Brand
Oct 21, 2006·The Journal of Clinical Investigation·Hang ShiJeffrey S Flier
Nov 9, 2006·American Journal of Physiology. Endocrinology and Metabolism·S J CreelyS Kumar
Dec 15, 2006·Nature·Gökhan S Hotamisligil
Jan 11, 2007·Biochemical and Biophysical Research Communications·Takayoshi SuganamiYoshihiro Ogawa
Feb 3, 2007·Proceedings of the National Academy of Sciences of the United States of America·Sunshin KimMyung-Shik Lee
Mar 21, 2007·The British Journal of Nutrition·Patrice D CaniNathalie M Delzenne
Mar 22, 2007·The Journal of Clinical Endocrinology and Metabolism·Paul D AndersonMuredach P Reilly
Apr 13, 2007·The New England Journal of Medicine·Claus M LarsenMarc Y Donath
Dec 1, 2007·Endocrine Reviews·Vincent Poitout, R Paul Robertson
Dec 20, 2007·Current Opinion in Clinical Nutrition and Metabolic Care·Patrice D Cani, Nathalie M Delzenne

❮ Previous
Next ❯

Citations

Feb 5, 2014·Immunology and Cell Biology·Clara Westwell-RoperJan A Ehses
Apr 18, 2014·Current Diabetes Reports·Rohit B Sharma, Laura C Alonso
Mar 15, 2013·Trends in Endocrinology and Metabolism : TEM·Yumi ImaiJerry L Nadler
Dec 12, 2012·Diabetes/metabolism Research and Reviews·Harsh PanwarSunita Grover
Oct 8, 2013·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Andrei Alexandru ConstantinescuLaurence Kessler
May 8, 2014·Mediators of Inflammation·Carmela Rita BalistreriRoberto Testa
Sep 9, 2015·Journal of Diabetes Research·Camila Leal-LopesRicardo G Correa
Jul 5, 2013·Endocrine Practice : Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists·Elena Barengolts
Jun 19, 2016·Lipids in Health and Disease·Othman A BaothmanMohamed Abu-Farha
Jan 31, 2014·Nutrition Journal·Kim-Tiu TengKalanithi Nesaretnam
Nov 25, 2014·Molecular Nutrition & Food Research·Estanislau NavarroHelmut Schröder
Mar 30, 2017·Experimental Cell Research·Nathalie Jouvet, Jennifer L Estall
Mar 23, 2018·Nutrients·Paloma Acosta-Montaño, Víctor García-González
Aug 10, 2017·International Journal of Obesity : Journal of the International Association for the Study of Obesity·L CrovesyM Soares-Mota
Jun 7, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Abhisek GhosalHamid M Said
Jul 15, 2015·American Journal of Physiology. Endocrinology and Metabolism·Robert H J BandsmaGary F Lewis
Nov 23, 2019·Current Diabetes Reports·Sandrine LevetD Hober
Dec 15, 2012·Endocrine Reviews·K H WilliamsS M Twigg
Oct 14, 2016·Journal of Cellular Biochemistry·Sunderajhan SekarIndira Prasadam
Mar 23, 2018·Mediators of Inflammation·D PagliariR Cianci
Dec 19, 2019·Frontiers in Bioengineering and Biotechnology·Ning SongShili Liu
Jan 20, 2017·Molecular Medicine Reports·Xiao WangChun Mei Huang
Oct 23, 2018·Stress : the International Journal on the Biology of Stress·Xingxing MoFan Bian
Aug 23, 2019·Annual Review of Nutrition·Timon E AdolphHerbert Tilg
Dec 31, 2014·World Journal of Gastroenterology : WJG·Jun-Ling Han, Hui-Ling Lin

❮ Previous
Next ❯

Methods Mentioned

BETA
density gradient centrifugation
transfections

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Antidiabetic Cellular Plasticity

This feed focuses on mechanisms that underlie cellular plasticity as a treatment for diabetes and other degenerative diseases.

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

Caspases in Metabolic Diseases

Caspases, the family of cysteine proteases are involved in programmed cell death, but their role in metabolic diseases, inflammation and immunity has been of interested. Discover the latest research on caspases in metabolic diseases here.