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Cell Metab. 2014 May 6;19(5):883-90. doi: 10.1016/j.cmet.2014.03.001. Epub 2014 Apr 10.

The complement inhibitor CD59 regulates insulin secretion by modulating exocytotic events.

Author information

1
Lund University Diabetes Center, Department of Clinical Sciences Malmö, Lund University, SE-205 02 Malmö, Sweden.
2
Department of Laboratory Medicine Malmö, Lund University, SE-205 02 Malmö, Sweden.
3
Department of Medical Cell Biology, Uppsala University, Box 571, SE-751 23 Uppsala, Sweden.
4
Department of Laboratory Medicine Malmö, Lund University, SE-205 02 Malmö, Sweden. Electronic address: anna.blom@med.lu.se.
5
Lund University Diabetes Center, Department of Clinical Sciences Malmö, Lund University, SE-205 02 Malmö, Sweden. Electronic address: erik.renstrom@med.lu.se.

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.

PMID:
24726385
DOI:
10.1016/j.cmet.2014.03.001
[Indexed for MEDLINE]
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