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Expression of transient receptor potential ankyrin 1 (TRPA1) and its role in insulin release from rat pancreatic beta cells.

Authors: Cao, DS  Zhong, L  Hsieh, TH  Abooj, M  Bishnoi, M  Hughes, L  Premkumar, LS 
Citation: Cao DS, etal., PLoS One. 2012;7(5):e38005. doi: 10.1371/journal.pone.0038005. Epub 2012 May 31.
Pubmed: (View Article at PubMed) PMID:22701540
DOI: Full-text: DOI:10.1371/journal.pone.0038005

OBJECTIVE: 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. METHODS: Immunohistochemistry, RT-PCR, and Western blot techniques were used to determine the expression of TRPA1 channel. Ca(2)(+) fluorescence imaging and electrophysiology (voltage- and current-clamp) techniques were used to study the channel properties. TRPA1-mediated insulin release was determined using ELISA. RESULTS: 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 (H(2)O(2)), 4-hydroxynonenal (4-HNE), and cyclopentenone prostaglandins (PGJ(2)) and a novel agonist methylglyoxal (MG) induces membrane current, depolarization, and Ca(2)(+) 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 Ca(2)(+) channel blockade as well as ATP sensitive potassium (K(ATP)) channel activation. CONCLUSIONS: We propose that endogenous and exogenous ligands of TRPA1 cause Ca(2)(+) influx and induce basal insulin release and that TRPA1-mediated depolarization acts synergistically with K(ATP) channel blockade to facilitate insulin release.

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CRRD Object Information
CRRD ID: 10043784
Created: 2015-05-27
Species: All species
Last Modified: 2015-05-27
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.