title: The neuronal Ca2+ sensor protein visinin-like protein-1 is expressed in pancreatic islets and regulates insulin secretion.
abstract: 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 beta-cells. To gain insight into the functions of VILIP-1 in beta-cells, we used both overexpression and small interfering RNA knockdown strategies. Overexpression of VILIP-1 in the MIN6 beta-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 beta-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 beta-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.
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Feihan F
authors.initials: FF
authors.lastname: Dai
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Youhou
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.affiliation: Signal Transduction Research Group, Neuroscience Research Center of the Charité, Universitätsmedizin Berlin, 10117 Berlin, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Braunewell
authors.affiliation: Department of Biomedical Sciences, University of Prince Edward Island, Charlottetown, Prince Edward Island C1A 4P3, Canada.
authors.forename: Catherine B
authors.initials: CB
authors.lastname: Chan
authors.affiliation: Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Electronic address: michael.wheeler@utoronto.ca.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wheeler
mesh_terms: D000818:Animals; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D005089:Exocytosis; D005786:Gene Expression Regulation; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051596:Neurocalcin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D007328:Insulin; D051596:Neurocalcin; D034741:RNA, Small Interfering; C496689:Vsnl1 protein, mouse; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases