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题名:Calcium/calmodulin-dependent serine protein kinase is involved in exendin-4-induced insulin secretion in INS-1 cells.
作者:ZHU ZQ; WANG D; XIANG D; YUAN YX; WANG Y;
来源:Metabolism. 2014 Jan;63(1):120-6. doi: 10.1016/j.metabol.2013.09.009. Epub 2013 [ IF= 0.00 ] ]
URL :10.1016/j.metabol.2013.09.009
日期:20140217
摘要: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
beta-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 beta-cell insulin
secretion by Ex-4 is mediated, at least in part, by CASK via a novel signaling
mechanism.

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