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A member of the neuronal Ca2+-sensor protein family visinin-like-protein-1 (vilip-1) is expressed in pancreatic β-cells and regulates insulin secretion and biosynthesis Open Access
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Dai, Feihan F.
Gaisano, Herbert Y.
Chan, Catherine B.
Wheeler, Michael B.
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Mechanisms of Signal Transduction
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- Journal Article (Published)
Visinin-like protein-1 (VILIP-1) is a member of the neuronal Ca2+ sensor protein family that modulates Ca2+-dependent cell signaling events. VILIP-1, which is expressed primarily in the brain, increases cAMP formation in neural cells by modulating adenylyl cyclase, but its functional role in other tissues remains largely unknown. In this study, we demonstrate that VILIP-1 is expressed in murine pancreatic islets and β-cells. To gain insight into the functions of VILIP-1 in β-cells, we used both overexpression and small interfering RNA knockdown strategies. Overexpression of VILIP-1 in the MIN6β-cell line or isolated mouse islets had no effect on basal insulin secretion but significantly increased glucose-stimulated insulin secretion. cAMP accumulation was elevated in VILIP-1-overexpressing cells, and the protein kinase A inhibitor H-89 attenuated increased glucose-stimulated insulin secretion. Overexpression of VILIP-1 in isolated mouse β-cells increased cAMP content accompanied by increased cAMP-responsive element-binding protein gene expression and enhanced exocytosis as detected by cell capacitance measurements. Conversely, VILIP-1 knockdown by small interfering RNA caused a reduction in cAMP accumulation and produced a dramatic increase in preproinsulin mRNA, basal insulin secretion, and total cellular insulin content. The increase in preproinsulin mRNA in these cells was attributed to enhanced insulin gene transcription. Taken together, we have shown that VILIP-1 is expressed in pancreatic β-cells and modulates insulin secretion. Increased VILIP-1 enhanced insulin secretion in a cAMP-associated manner. Down-regulation of VILIP-1 was accompanied by decreased cAMP accumulation but increased insulin gene transcription.
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- © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.
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Dai, F., Zhang, Y., Kang, Y., Wang, Q., Gaisano, H. Y., Braunewell, K. H., Chan, C. B., & Wheeler, M. B. (2006). A member of the neuronal Ca2+-sensor protein family visinin-like-protein-1 (vilip-1) is expressed in pancreatic β-cells and regulates insulin secretion and biosynthesis. Journal of Biological Chemistry, 281(31), 21942-21953. http://dx.doi.org/10.1074/jbc.M512924200
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