Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells.
Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells.
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DOI：
10.1371/journal.pone.0038005
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Premkumar LS
中科院分区：
文献类型：
--
作者：
Cao DS;Zhong L;Hsieh TH;Abooj M;Bishnoi M;Hughes L;Premkumar LS
Several transient receptor potential (TRP) channels are expressed in pancreatic beta cells and have been proposed to be involved in insulin secretion. However, the endogenous ligands for these channels are far from clear. Here, we demonstrate the expression of the transient receptor potential ankyrin 1 (TRPA1) ion channel in the pancreatic beta cells and its role in insulin release. TRPA1 is an attractive candidate for inducing insulin release because it is calcium permeable and is activated by molecules that are produced during oxidative glycolysis. Immunohistochemistry, RT-PCR, and Western blot techniques were used to determine the expression of TRPA1 channel. Ca2+ fluorescence imaging and electrophysiology (voltage- and current-clamp) techniques were used to study the channel properties. TRPA1-mediated insulin release was determined using ELISA. TRPA1 is abundantly expressed in a rat pancreatic beta cell line and freshly isolated rat pancreatic beta cells, but not in pancreatic alpha cells. Activation of TRPA1 by allyl isothiocyanate (AITC), hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE), and cyclopentenone prostaglandins (PGJ2) and a novel agonist methylglyoxal (MG) induces membrane current, depolarization, and Ca2+ influx leading to generation of action potentials in a pancreatic beta cell line and primary cultured pancreatic beta cells. Activation of TRPA1 by agonists stimulates insulin release in pancreatic beta cells that can be inhibited by TRPA1 antagonists such as HC030031 or AP-18 and by RNA interference. TRPA1-mediated insulin release is also observed in conditions of voltage-gated Na+ and Ca2+ channel blockade as well as ATP sensitive potassium (KATP) channel activation. We propose that endogenous and exogenous ligands of TRPA1 cause Ca2+ influx and induce basal insulin release and that TRPA1-mediated depolarization acts synergistically with KATP channel blockade to facilitate insulin release.
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DOI：
10.1006/bbrc.1995.1149
发表时间：
1995-02-06
影响因子：
3.1
作者：
BRITSCH, S;KRIPPEITDREWS, P;DREWS, G
通讯作者：
DREWS, G
DOI：
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发表时间：
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期刊：
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作者：
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DOI：
10.1016/j.bbrc.2004.06.149
发表时间：
2004-08-11
影响因子：
3.1
作者：
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通讯作者：
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DOI：
10.1007/978-94-007-0265-3_42
发表时间：
2011-01-01
期刊：
TRANSIENT RECEPTOR POTENTIAL CHANNELS
影响因子：
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作者：
Islam, Md Shahidul
通讯作者：
Islam, Md Shahidul
影响因子：
15.9
作者：
Bessac, Bret F.;Sivula, Michael;Jordt, Sven-Eric
通讯作者：
Jordt, Sven-Eric