title: Nesfatin-1 enhances glucose-induced insulin secretion by promoting Ca(2+) influx through L-type channels in mouse islet β-cells.
abstract: Nucleobindin-2 (NUCB2)-derived nesfatin-1 located in the brain has been implicated in the satiety and control of energy metabolism. Nesfatin-1 is also produced in the periphery and present in the plasma. It has recently been reported that NUCB2/nesfatin-1 is localized in pancreatic islet β-cells in mice and rats and released from islets. However, its function in islets remains largely unknown. This study examined direct effects of nesfatin-1 on insulin release from pancreatic islets and on cytosolic Ca(2+) concentration ([Ca(2+)](i)) in single β-cells from ICR mice. In the presence of 8.3 mmol/L glucose, nesfatin-1 at 10(-10)-10(-9) mol/L tended to increase and at 10(-8) mol/L increased insulin release from isolated islets, while at 2.8 mmol/L glucose nesfatin-1 had no effect. Furthermore, nesfatin-1 at 10(-10)-10(-8) mol/L increased [Ca(2+)](i) in single β-cells in the presence of 8.3 but not 2.8 mmol/L glucose. The nesfatin-1-induced [Ca(2+)](i) increase and insulin release were inhibited by removal of extracellular Ca(2+) and by addition of nitrendipine, a blocker of voltage-dependent L-type Ca(2+) channels. Unexpectedly, the [Ca(2+)](i) responses to nesfatin-1 were unaltered by inhibitors of protein kinase A (PKA) and phospholipase A(2) (PLA(2)). These results indicate that nesfain-1 potentiates glucose-induced insulin secretion by promoting Ca(2+) influx through L-type Ca(2+) channels independently of PKA and PLA(2) in mouse islet β-cells.
authors.affiliation: Department of Physiology, Division of Integrative Physiology, Jichi Medical University School of Medicine, Shimotsuke, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakata
authors.forename: Kazunori
authors.initials: K
authors.lastname: Manaka
authors.forename: Sawako
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000502:physiology*; D002135:Calcium-Binding Proteins; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000080866:Nucleobindins; D054467:Phospholipases A2 / Q000378:metabolism
chemical_list: D020746:Calcium Channels, L-Type; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D017868:Cyclic AMP-Dependent Protein Kinases; D054467:Phospholipases A2; D005947:Glucose; D002118:Calcium