Interleukin-6 regulates pancreatic alpha-cell mass expansion.

Proceedings of the National Academy of Sciences of the United States of America
Helga EllingsgaardMarc Y Donath

Abstract

Interleukin-6 (IL-6) is systemically elevated in obesity and is a predictive factor to develop type 2 diabetes. Pancreatic islet pathology in type 2 diabetes is characterized by reduced beta-cell function and mass, an increased proportion of alpha-cells relative to beta-cells, and alpha-cell dysfunction. Here we show that the alpha cell is a primary target of IL-6 actions. Beginning with investigating the tissue-specific expression pattern of the IL-6 receptor (IL-6R) in both mice and rats, we find the highest expression of the IL-6R in the endocrine pancreas, with highest expression on the alpha-cell. The islet IL-6R is functional, and IL-6 acutely regulates both pro-glucagon mRNA and glucagon secretion in mouse and human islets, with no acute effect on insulin secretion. Furthermore, IL-6 stimulates alpha-cell proliferation, prevents apoptosis due to metabolic stress, and regulates alpha-cell mass in vivo. Using IL-6 KO mice fed a high-fat diet, we find that IL-6 is necessary for high-fat diet-induced increased alpha-cell mass, an effect that occurs early in response to diet change. Further, after high-fat diet feeding, IL-6 KO mice without expansion of alpha-cell mass display decreased fasting glucagon levels. However, despi...Continue Reading

References

May 1, 1983·Diabetologia·D E McMillan
May 1, 1983·Diabetologia·J RahierJ C Henquin
Jun 20, 1998·The Journal of Physiology·K OstrowskiB K Pedersen
Aug 16, 2001·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·R KurotaniR Y Osamura
Jan 12, 2002·Nature Medicine·Ville WalleniusJohn-Olov Jansson
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Kathrin MaedlerMarc Y Donath
Apr 11, 2003·Reviews of Physiology, Biochemistry and Pharmacology·D KamimuraT Hirano
May 3, 2003·The Journal of Clinical Endocrinology and Metabolism·Kun Ho YoonSusan Bonner-Weir
Nov 12, 2003·Journal of Muscle Research and Cell Motility·B K PedersenB Saltin
Jun 12, 2004·American Journal of Physiology. Endocrinology and Metabolism·Gina B Di GregorioPhilip A Kern
Dec 29, 2004·Regulatory Peptides·Haruaki KageyamaSeiji Shioda
Nov 25, 2005·Diabetes·Marc Y DonathManfred Reinecke
Oct 28, 2006·Journal of Applied Physiology·Bente K Pedersen, Mark A Febbraio
Jan 31, 2007·Endocrine Reviews·Jesper GromadaClaes B Wollheim
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Desiree M SchumannMarc Y Donath
Apr 13, 2007·The New England Journal of Medicine·Claus M LarsenMarc Y Donath
Jun 21, 2007·Diabetes·Jan A EhsesMarc Y Donath
Sep 12, 2007·Diabetologia·E FerranniniUNKNOWN Relationship between Insulin Sensitivity and Cardiovascular Disease Risk (RISC) Project Investigators
Apr 26, 2008·Endocrine Reviews·Stephanie T PageWilliam J Bremner

❮ Previous
Next ❯

Citations

Jun 5, 2012·European Journal of Nutrition·Bianca Martins GregorioMarcia Barbosa Aguila
Dec 12, 2012·International Journal of Obesity : Journal of the International Association for the Study of Obesity·R Guardado-MendozaF Folli
Aug 17, 2011·Diabetes, Obesity & Metabolism·D KawamoriR N Kulkarni
Aug 17, 2011·Diabetes, Obesity & Metabolism·Y Hayashi
Sep 7, 2012·Diabetes, Obesity & Metabolism·P PlomgaardK Bouzakri
Dec 15, 2010·Journal of Veterinary Internal Medicine·F TschuorC E Reusch
Jun 11, 2009·Physiology·Stephanie Z Young, Angélique Bordey
Aug 13, 2010·The Review of Diabetic Studies : RDS·Josiane CoulaudFrancoise Homo-Delarche
Feb 21, 2014·Seminars in Immunology·Koji Taniguchi, Michael Karin
Mar 29, 2014·Diabetologia·Kristin EckardtJürgen Eckel
Feb 5, 2014·Immunology and Cell Biology·Clara Westwell-RoperJan A Ehses
May 16, 2014·Diabetologia·Teresa Mezza, Rohit N Kulkarni
Apr 12, 2014·Nutrition Research Reviews·Laura MarroquíIvan Quesada
Jan 6, 2012·Acta Diabetologica·Alberto M DavalliFranco B Folli
Jan 7, 2011·Proceedings. Biological Sciences·Manos TsakirisMarcello Costantini
Aug 4, 2009·Archives of Physiology and Biochemistry·Jan A EhsesMarc Y Donath
Dec 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Danny Ben-ZviDouglas A Melton
Nov 17, 2015·Immunology and Cell Biology·Kristian Karstoft, Bente Klarlund Pedersen
Oct 18, 2014·Islets·M A Russell, N G Morgan
Sep 1, 2015·Experimental Cell Research·Maren G DietrichMarkus Niessen
Jun 28, 2012·Journal of Toxicology·Linda Christian Carrijo-CarvalhoAna Marisa Chudzinski-Tavassi
Feb 14, 2012·Expert Opinion on Therapeutic Targets·Georg H Waetzig, Stefan Rose-John
Aug 1, 2012·Islets·Joel F Habener, Violeta Stanojevic
Dec 19, 2012·General and Comparative Endocrinology·M OstoT A Lutz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Auditory Perception

Auditory perception is the ability to receive and interpret information attained by the ears. Here is the latest research on factors and underlying mechanisms that influence auditory perception.

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