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The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.

Author:
  • Ulrika Krus
  • Ben King
  • Vini Nagaraj
  • Nikhil R Gandasi
  • Jonatan Sjölander
  • Pawel Buda
  • Eliana Garcia Vaz
  • Maria Gomez
  • Emilia Ottosson Laakso
  • Petter Storm
  • Malin Fex
  • Petter Vikman
  • Enming Zhang
  • Sebastian Barg
  • Anna Blom
  • Erik Renström
Publishing year: 2014
Language: English
Pages: 883-890
Publication/Series: Cell Metabolism
Volume: 19
Issue: 5
Document type: Journal article
Publisher: Cell Press

Abstract english

Type 2 diabetes is triggered by reduced insulin production, caused by genetic and environmental factors such as inflammation originating from the innate immune system. Complement proteins are a component of innate immunity and kill non-self cells by perforating the plasma membrane, a reaction prevented by CD59. Human pancreatic islets express CD59 at very high levels. CD59 is primarily known as a plasma membrane protein in membrane rafts, but most CD59 protein in pancreatic β cells is intracellular. Removing extracellular CD59 disrupts membrane rafts and moderately stimulates insulin secretion, whereas silencing intracellular CD59 markedly suppresses regulated secretion by exocytosis, as demonstrated by TIRF imaging. CD59 interacts with the exocytotic proteins VAMP2 and Syntaxin-1. CD59 expression is reduced by glucose and in rodent diabetes models but upregulated in human diabetic islets, potentially reflecting compensatory reactions. This unconventional action of CD59 broadens the established view of innate immunity in type 2 diabetes.

Keywords

  • Cell and Molecular Biology

Other

Published
  • Islet patophysiology
  • Protein Chemistry, Malmö
  • Diabetes and Endocrinology
  • Diabetes and Celiac Unit
  • Islet cell physiology
  • ISSN: 1550-4131
Erik Renström
E-mail: erik.renstrom [at] med.lu.se

Deputy head of department

Department of Clinical Sciences, Malmö

+46 40 39 11 57

+46 40 39 11 57

Principal investigator

Islet patophysiology

+46 40 39 11 57

+46 40 39 11 57

20-3-308

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Lund University Diabetes Centre, CRC, SUS Malmö, Entrance 72, House 91:12. SE-205 02 Malmö. Telephone: +46 40 39 10 00