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

Krus, Ulrika LU ; King, Ben LU ; Nagaraj, Vini LU ; Gandasi, Nikhil R; Sjölander, Jonatan LU ; Buda, Pawel LU ; Garcia Vaz, Eliana LU ; Gomez, Maria LU ; Ottosson Laakso, Emilia LU and Storm, Petter LU , et al. (2014) In Cell Metabolism 19(5). p.883-890
Abstract
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... (More)
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. (Less)
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type
Contribution to journal
publication status
published
subject
in
Cell Metabolism
volume
19
issue
5
pages
883 - 890
publisher
Cell Press
external identifiers
  • pmid:24726385
  • wos:000335561200016
  • scopus:84900310298
ISSN
1550-4131
DOI
10.1016/j.cmet.2014.03.001
language
English
LU publication?
yes
id
c31c2961-359d-4efb-830c-f53e8d643b54 (old id 4430237)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24726385?dopt=Abstract
date added to LUP
2014-05-05 20:41:58
date last changed
2017-08-20 03:07:37
@article{c31c2961-359d-4efb-830c-f53e8d643b54,
  abstract     = {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.},
  author       = {Krus, Ulrika and King, Ben and Nagaraj, Vini and Gandasi, Nikhil R and Sjölander, Jonatan and Buda, Pawel and Garcia Vaz, Eliana and Gomez, Maria and Ottosson Laakso, Emilia and Storm, Petter and Fex, Malin and Vikman, Petter and Zhang, Enming and Barg, Sebastian and Blom, Anna and Renström, Erik},
  issn         = {1550-4131},
  language     = {eng},
  number       = {5},
  pages        = {883--890},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2014.03.001},
  volume       = {19},
  year         = {2014},
}