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Diabetologia
Published in: Diabetologia 10/2011

01-10-2011 | Article

Rat pancreatic level of cystathionine γ-lyase is regulated by glucose level via specificity protein 1 (SP1) phosphorylation

Authors: L. Zhang, G. Yang, G. Tang, L. Wu, R. Wang

Published in: Diabetologia | Issue 10/2011

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Abstract

Aims/hypothesis

Cystathionine γ-lyase (CSE) catalyses the endogenous production of hydrogen sulphide (H2S) in pancreatic beta cells, and H2S has been shown to inhibit insulin release from these cells. As altered pancreatic H2S production modulated by glucose has been previously shown, we hypothesised that the Cse gene could be regulated by glucose level in insulin-secreting cells.

Methods

The effects of glucose on CSE protein level and mRNA level were analysed in INS-1E cells. Glucose effect on Cse promoter activity was tested by constructing a proximal Cse promoter vector including specificity protein 1 (Sp1) consensus sequence.

Results

High glucose (20 mmol/l) inhibited H2S production in INS-1E cells and freshly isolated rat pancreatic islets. Cse mRNA expression, CSE activity and protein abundance were also profoundly reduced by high glucose. The involvement of SP1 in basal and high-glucose-regulated CSE production was demonstrated. Sp1-knockdown abolished a large portion of CSE production at basal glucose. Phosphorylation of SP1 stimulated by high glucose was inhibited by p38 mitogen-activated protein kinase (MAPK) inhibitors SB203580 and SB202190. After blocking p38 MAPK phosphorylation, the inhibitive effects of high glucose on CSE protein production and promoter activity in INS-1E cells were also virtually abolished.

Conclusions/interpretation

Glucose stimulates the phosphorylation of SP1 via p38 MAPK activation, which leads to decreased Cse promoter activity and subsequent downregulation of Cse gene expression. Inhibited H2S production through glucose-mediated CSE activity and production alterations may be involved in the fine control of glucose-induced insulin secretion.
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Metadata
Title
Rat pancreatic level of cystathionine γ-lyase is regulated by glucose level via specificity protein 1 (SP1) phosphorylation
Authors
L. Zhang
G. Yang
G. Tang
L. Wu
R. Wang
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 10/2011
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-011-2187-4

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