The Complement Inhibitor CD59 Regulates Insulin Secretion by Modulating Exocytotic Events.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4430237
- author
- organization
-
- Diabetes - Islet Patophysiology (research group)
- Protein Chemistry, Malmö (research group)
- Diabetic Complications (research group)
- Translational Muscle Research (research group)
- Celiac Disease and Diabetes Unit (research group)
- Islet cell physiology (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- publishing date
- 2014
- 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
- 2016-04-01 10:09:10
- date last changed
- 2024-05-05 05:55:02
@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 = {{https://lup.lub.lu.se/search/files/1608398/4732318.pdf}}, doi = {{10.1016/j.cmet.2014.03.001}}, volume = {{19}}, year = {{2014}}, }