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Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4-induced insulin secretion in INS-1 cells.

Authors: Zhu, Zheng-Qiu  Wang, Dong  Xiang, Dan  Yuan, Yue-Xing  Wang, Yao 
Citation: Zhu ZQ, etal., Metabolism. 2014 Jan;63(1):120-6. doi: 10.1016/j.metabol.2013.09.009. Epub 2013 Oct 17.
Pubmed: (View Article at PubMed) PMID:24140090
DOI: Full-text: DOI:10.1016/j.metabol.2013.09.009

OBJECTIVE: Exendin-4 (Ex-4) is an anti-diabetic drug that is a potent agonist of the glucagon-like peptide-1 (GLP-1) receptor. It has already been approved for the treatment of type 2 diabetes mellitus, but its underlying mechanisms of action are not fully understood. Calcium/calmodulin-dependent serine protein kinase (CASK), which plays a vital role in the transport and release of neurotransmitters in neurons, is expressed in pancreatic islet cells and ß-cells. This study aimed to investigate whether CASK is involved in the insulin secretagogue action induced by Ex-4 in INS-1 cells.
MATERIAL/METHODS: A glucose-stimulated insulin secretion (GSIS) assay was performed with or without siRNA treatment against CASK. The expression level and location of CASK were evaluated by real-time PCR, western blotting and immunofluorescence. With the use of a protein kinase A (PKA) inhibitor or an exchange protein directly activated by cAMP-2 (Epac2) agonist, immunoblotting was performed to establish the signaling pathway through which Ex-4 alters CASK expression.
RESULTS: Knock-down of CASK significantly attenuated the Ex-4-enhanced insulin release, and we showed that Ex-4 could increase transcription of CASK mRNA and expression of CASK protein but did not change the cellular location of CASK. A PKA inhibitor reduced the ability of Ex-4 to stimulate CASK expression, but an Epac2 agonist had no effect suggesting that regulation was mediated by the cAMP/PKA pathway.
CONCLUSION: Our study suggests that the stimulation of ß-cell insulin secretion by Ex-4 is mediated, at least in part, by CASK via a novel signaling mechanism.


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CRRD Object Information
CRRD ID: 11576293
Created: 2017-01-05
Species: All species
Last Modified: 2017-01-05
Status: ACTIVE


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