title: Nutrient responsive nesfatin-1 regulates energy balance and induces glucose-stimulated insulin secretion in rats.
abstract: Nesfatin-1 is a recently discovered anorexigen, and we first reported nesfatin-like immunoreactivity in the pancreatic β-cells. The aim of this study was to characterize the effects of nesfatin-1 on whole-body energy homeostasis, insulin secretion, and glycemia. The in vivo effects of continuous peripheral delivery of nesfatin-1 using osmotic minipumps on food intake and substrate partitioning were examined in ad libitum-fed male Fischer 344 rats. The effects of nesfatin-1 on glucose-stimulated insulin secretion (GSIS) were examined in isolated pancreatic islets. L6 skeletal muscle cells and isolated rat adipocytes were used to assess the effects of nesfatin-1 on basal and insulin-mediated glucose uptake as well as on major steps of insulin signaling in these cells. Nesfatin-1 reduced cumulative food intake and increased spontaneous physical activity, whole-body fat oxidation, and carnitine palmitoyltransferase I mRNA expression in brown adipose tissue but did not affect uncoupling protein 1 mRNA in the brown adipose tissue. Nesfatin-1 significantly enhanced GSIS in vivo during an oral glucose tolerance test and improved insulin sensitivity. Although insulin-stimulated glucose uptake in L6 muscle cells was inhibited by nesfatin-1 pretreatment, basal and insulin-induced glucose uptake in adipocytes from nesfatin-1-treated rats was significantly increased. In agreement with our in vivo results, nesfatin-1 enhanced GSIS from isolated pancreatic islets at both normal (5.6 mM) and high (16.7 mM), but not at low (2 mM), glucose concentrations. Furthermore, nesfatin-1/nucleobindin 2 release from rat pancreatic islets was stimulated by glucose. Collectively, our data indicate that glucose-responsive nesfatin-1 regulates insulin secretion, glucose homeostasis, and whole-body energy balance in rats.
authors.affiliation: Laboratory of Integrative Neuroendocrinology, Department of Biology, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3.
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez
authors.forename: R L S
authors.initials: RL
authors.lastname: Perry
authors.forename: X
authors.initials: X
authors.lastname: Gao
authors.forename: M P
authors.initials: MP
authors.lastname: Gaidhu
authors.forename: R G
authors.initials: RG
authors.lastname: Tsushima
authors.forename: R B
authors.initials: RB
authors.lastname: Ceddia
authors.forename: S
authors.initials: S
authors.lastname: Unniappan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000097:blood / Q000502:physiology*; D000080866:Nucleobindins; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose