title: SIDT2 is involved in the NAADP-mediated release of calcium from insulin secretory granules.
abstract: The Sidt2 global knockout mouse (Sidt2(-/-)) has impaired insulin secretion. The aim of this study was to assess the role of SIDT2 protein in glucose-induced insulin secretion in primary cultured mouse β-cells. The major metabolic and electrophysiological steps of glucose-induced insulin secretion of primary cultured β-cells from Sidt2(-/-) mice were investigated. The β-cells from Sidt2(-/-) mice had normal NAD(P)H responses and KATP and KV currents. However, they exhibited a lower [Ca(2+)]i peak height when stimulated with 20mM glucose compared with those from WT mice. Furthermore, it took a longer time for the [Ca(2+)]i of β-cell from Sidt2(-/-) mice to reach the peak. Pretreatment with ryanodine or 2-aminoethoxydiphenyl borate (2-APB) did not change [Ca(2+)]i the response pattern to glucose in Sidt2(-/-) cells. Extraordinarily, pretreatment with bafilomycin A1(Baf-A1) led to a comparable [Ca(2+)]i increase pattern between these two groups, suggesting that calcium traffic from the intracellular acidic compartment is defective in Sidt2(-/-) β-cells. Bath-mediated application of 50nM nicotinic acid adenine dinucleotide phosphate (NAADP) normalized the [Ca(2+)]i response of Sidt2(-/-) β-cells. Finally, glucose-induced CD38 expression increased to a comparable level between Sidt2(-/-) and WT islets, suggesting that Sidt2(-/-) islets generated NAADP normally. We conclude that Sidt2 is involved in NAADP-mediated release of calcium from insulin secretory granules and thus regulates insulin secretion.
authors.affiliation: Department of Pediatric Endocrinology and Genetic MetabolismXinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Guoying
authors.initials: G
authors.lastname: Chang
authors.affiliation: Department of Pediatric Endocrinology and Genetic MetabolismXinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Shanghai Clinical Center for Endocrine and Metabolic DiseasesShanghai Key Laboratory for Endocrine Tumors, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Aifang
authors.initials: A
authors.lastname: Nie
authors.affiliation: Department of Pediatric Endocrinology and Genetic MetabolismXinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China huiwenzhang@yahoo.com gu_xuefan@163.com.
authors.forename: Xuefan
authors.initials: X
authors.lastname: Gu
authors.affiliation: Department of Pediatric Endocrinology and Genetic MetabolismXinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China huiwenzhang@yahoo.com gu_xuefan@163.com.
authors.forename: Huiwen
authors.initials: H
authors.lastname: Zhang
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D015870:Gene Expression; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009249:NADP / Q000031:analogs & derivatives* / Q000378:metabolism; D033704:Nucleotide Transport Proteins; D021381:Protein Transport; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D007328:Insulin; D008565:Membrane Proteins; D033704:Nucleotide Transport Proteins; C554947:Sidt2 protein, mouse; D009249:NADP; C024376:NAADP; D051997:ADP-ribosyl Cyclase 1; D005947:Glucose; D002118:Calcium
keywords: CD38; Ca2+; NAADP; Sidt2; insulin secretory granule