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Redox control of exocytosis - Regulatory role of NADPH, thioredoxin, and glutaredoxin

Ivarsson, Rosita LU ; Quintens, R; Dejonghe, S; Tsukamoto, K; Veld, P; Renström, Erik LU and Schuit, FC (2005) In Diabetes 54(7). p.2132-2142
Abstract
Cellular redox state is an important metabolic variable, influencing many aspects of cell function like growth, apoptosis, and reductive biosynthesis. In this report, we identify NADPH as a candidate signaling molecule for exocytosis in neuroendocrine cells. In pancreatic beta-cells, glucose acutely raised the NADPH-to-NADP(+) ratio and stimulated insulin release in parallel. Furthermore, intracellular addition of NADPH directly stimulated exocytosis of insulin granules. Effects of NADPH on exocytosis are proposed to be mediated by the redox proteins glutaredoxin (GRX) and thioredoxin (TRX) on the basis of the following evidence: 1) Expression of GRX mRNA is very high in beta-cells compared with other studied tissues, and GRX protein... (More)
Cellular redox state is an important metabolic variable, influencing many aspects of cell function like growth, apoptosis, and reductive biosynthesis. In this report, we identify NADPH as a candidate signaling molecule for exocytosis in neuroendocrine cells. In pancreatic beta-cells, glucose acutely raised the NADPH-to-NADP(+) ratio and stimulated insulin release in parallel. Furthermore, intracellular addition of NADPH directly stimulated exocytosis of insulin granules. Effects of NADPH on exocytosis are proposed to be mediated by the redox proteins glutaredoxin (GRX) and thioredoxin (TRX) on the basis of the following evidence: 1) Expression of GRX mRNA is very high in beta-cells compared with other studied tissues, and GRX protein expression is high in islets and in brain; 2) GRX and TRX are localized in distinct microdomains in the cytosol of beta-cells; and 3) microinjection of recombinant GRX potentiated effects of NADPH on exocytosis, whereas TRX antagonized the NADPH effect. We propose that the NADPEVGRX/ TRX redox regulation mediates a novel signaling pathway of nutrient-induced insulin secretion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
54
issue
7
pages
2132 - 2142
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000230164000028
  • pmid:15983215
  • scopus:21344456969
ISSN
1939-327X
language
English
LU publication?
yes
id
ee5cb630-a669-46ac-8517-28a97f15b2e5 (old id 233890)
alternative location
http://diabetes.diabetesjournals.org/cgi/content/full/54/7/2132
date added to LUP
2007-08-23 16:21:19
date last changed
2017-10-29 04:10:44
@article{ee5cb630-a669-46ac-8517-28a97f15b2e5,
  abstract     = {Cellular redox state is an important metabolic variable, influencing many aspects of cell function like growth, apoptosis, and reductive biosynthesis. In this report, we identify NADPH as a candidate signaling molecule for exocytosis in neuroendocrine cells. In pancreatic beta-cells, glucose acutely raised the NADPH-to-NADP(+) ratio and stimulated insulin release in parallel. Furthermore, intracellular addition of NADPH directly stimulated exocytosis of insulin granules. Effects of NADPH on exocytosis are proposed to be mediated by the redox proteins glutaredoxin (GRX) and thioredoxin (TRX) on the basis of the following evidence: 1) Expression of GRX mRNA is very high in beta-cells compared with other studied tissues, and GRX protein expression is high in islets and in brain; 2) GRX and TRX are localized in distinct microdomains in the cytosol of beta-cells; and 3) microinjection of recombinant GRX potentiated effects of NADPH on exocytosis, whereas TRX antagonized the NADPH effect. We propose that the NADPEVGRX/ TRX redox regulation mediates a novel signaling pathway of nutrient-induced insulin secretion.},
  author       = {Ivarsson, Rosita and Quintens, R and Dejonghe, S and Tsukamoto, K and Veld, P and Renström, Erik and Schuit, FC},
  issn         = {1939-327X},
  language     = {eng},
  number       = {7},
  pages        = {2132--2142},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Redox control of exocytosis - Regulatory role of NADPH, thioredoxin, and glutaredoxin},
  volume       = {54},
  year         = {2005},
}