title: Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats.
abstract: BACKGROUND
  Visfatin/PBEF/Nampt is an adipose-derived hormone proposed to exert insulin-mimicking effects and play a positive role in attenuating insulin resistance. However, the precise mechanisms underlying the beneficial effects of visfatin/PBEF/Nampt on insulin sensitivity remain unknown.
  
  
  METHODS
  Euglycemic-hyperinsulinemic clamps were used in the same groups of rats to study the in vivo effect of visfatin/PBEF/Nampt on insulin sensitivity and glucose/lipid metabolism before and after the overexpression of visfatin/PBEF/Nampt protein, which was carried out by injection of pcDNA3.1-visfatin plasmid.
  
  
  RESULTS
  On day 4 after plasmid injection, plasma visfatin/PBEF/Nampt protein levels were significantly increased and displayed a hypocholesterolemic effect in both normal-chow (NC) and high-fat diet (HT) animals with pcDNA3.1-visfatin treatment. A second glucose clamp also demonstrated increased insulin sensitivity in pcDNA3.1-visfatin animals. Consistent with the clamp data, the extent of insulin receptor substrate (IRS)-1 tyrosine phosphorylation in response to insulin was significantly enhanced in the liver and adipose tissues. In addition, the mRNA expression of peroxisome proliferator-activated receptor-gamma (PPARgamma) and sterol regulatory element-binding proteins 2 (SREBP-2) in the liver and adipose tissues was also significantly upregulated in these animals.
  
  
  CONCLUSIONS
  These results demonstrate that visfatin/PBEF/Nampt improves insulin sensitivity and exerts its hypocholesterolemic effects at least partially through upregulation of the tyrosine phosphorylation of IRS-1 protein and the mRNA levels of PPARgamma and SREBP-2.
authors.affiliation: Department of Endocrinology, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Renzhe
authors.initials: R
authors.lastname: Li
authors.forename: Mengliu
authors.initials: M
authors.lastname: Yang
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Nowicki
authors.forename: Haihong
authors.initials: H
authors.lastname: Zong
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Gangyi
authors.initials: G
authors.lastname: Yang
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
chemical_list: D016207:Cytokines; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D047495:PPAR gamma; D012333:RNA, Messenger; C470194:Srebf2 protein, rat; D051779:Sterol Regulatory Element Binding Proteins; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D054409:Nicotinamide Phosphoribosyltransferase; C504970:nicotinamide phosphoribosyltransferase, rat; D005947:Glucose