title: Peripheral effects of nesfatin-1 on glucose homeostasis.
abstract: OBJECTIVE
  The actions of peripherally administered nesfatin-1 on glucose homeostasis remain controversial. The aim of this study was to characterize the mechanisms by which peripheral nesfatin-1 regulates glucose metabolism.
  
  
  METHODS
  The effects of nesfatin-1 on glucose metabolism were examined in mice by continuous infusion of the peptide via osmotic pumps. Changes in AKT phosphorylation and Glut4 were investigated by Western blotting and immnuofluorescent staining. Primary myocytes, adipocytes and hepatocytes were isolated from male mice.
  
  
  RESULTS
  Continuous peripheral infusion of nesfatin-1 altered glucose tolerance and insulin sensitivity in mice fed either normal or high fat diet, while central administration of nesfatin-1 demonstrated no effect. Nesfatin-1 increases insulin secretion in vivo, and in vitro in cultured min6 cells. In addition, nesfatin-1 up-regulates the phosphorylation of AKT in pancreas and min6 islet cells. In mice fed normal diet, peripheral nesfatin-1 significantly increased insulin-stimulated phosphorylation of AKT in skeletal muscle, adipose tissue and liver; similar effects were observed in skeletal muscle and adipose tissue in mice fed high fat diet. At basal conditions and after insulin stimulation, peripheral nesfatin-1 markedly increased GLUT4 membrane translocation in skeletal muscle and adipose tissue in mice fed either diet. In vitro studies showed that nesfatin-1 increased both basal and insulin-stimulated levels of AKT phosphorylation in cells derived from skeletal muscle, adipose tissue and liver.
  
  
  CONCLUSIONS
  Our studies demonstrate that nesfatin-1 alters glucose metabolism by mechanisms which increase insulin secretion and insulin sensitivity via altering AKT phosphorylation and GLUT 4 membrane translocation in the skeletal muscle, adipose tissue and liver.
authors: Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.
authors: Ziru
authors: Z
authors: Li
authors: Ling
authors: L
authors: Gao
authors: Hong
authors: H
authors: Tang
authors: Yue
authors: Y
authors: Yin
authors: Xinxin
authors: X
authors: Xiang
authors: Yin
authors: Y
authors: Li
authors: Jing
authors: J
authors: Zhao
authors: Michael
authors: M
authors: Mulholland
authors: Weizhen
authors: W
authors: Zhang
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D002135:Calcium-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D000080866:Nucleobindins; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: D001786:Blood Glucose; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D009419:Nerve Tissue Proteins; C000630651:Nucb1 protein, mouse; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
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