title: Nesfatin-1 exerts a direct, glucose-dependent insulinotropic action on mouse islet β- and MIN6 cells.
abstract: Nesfatin-1 is a recently discovered multifunctional metabolic hormone abundantly expressed in the pancreatic islets. The main objective of this study is to characterize the direct effects of nesfatin-1 on insulin secretion in vitro using MIN6 cells and islets isolated from C57BL/6 mice. We also examined the expression of the nesfatin-1 precursor protein, nucleobindin 2 (NUCB2) mRNA, and nesfatin-1 immunoreactivity (ir) in the islets of normal mice and in the islets from mice with streptozotocin-induced type 1 diabetes and diet-induced obese (DIO) mice with type 2 diabetes. Nesfatin-1 stimulated glucose-induced insulin release in vitro from mouse islets and MIN6 cells in a dose-dependent manner. No such stimulation in insulin secretion was found when MIN6 cells/islets were incubated with nesfatin-1 in low glucose. In addition, a fourfold increase in nesfatin-1 release from MIN6 cells was observed following incubation in high glucose (16.7  mM) compared to low glucose (2  mM). Furthermore, we observed a significant reduction in both NUCB2 mRNA expression and nesfatin-1-ir in the pancreatic islets of mice with type 1 diabetes, while a significant increase was observed in the islets of DIO mice. Together, our findings indicate that nesfatin-1 is a novel insulinotropic peptide and that the endogenous pancreatic islet NUCB2/nesfatin is altered in diabetes and diet-induced obesity.
authors.affiliation: Laboratory of Integrative Neuroendocrinology Department of Biology School of Kinesiology and Health Sciences, York University, Toronto, Ontario, Canada.
authors.forename: Ronald
authors.initials: R
authors.lastname: Gonzalez
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Reingold
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Gao
authors.forename: Mandeep P
authors.initials: MP
authors.lastname: Gaidhu
authors.forename: Robert G
authors.initials: RG
authors.lastname: Tsushima
authors.forename: Suraj
authors.initials: S
authors.lastname: Unniappan
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism* / Q000494:pharmacology; D000080866:Nucleobindins; D009765:Obesity / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; D000080866:Nucleobindins; D005934:Glucagon; D005947:Glucose