Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats

Ann Med. 2009;41(4):311-20. doi: 10.1080/07853890902729760.


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.

Method: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism*
  • Fibroblast Growth Factors / metabolism
  • Gene Expression
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Insulin / metabolism*
  • Insulin Receptor Substrate Proteins / metabolism
  • Insulin Resistance*
  • Lipid Metabolism*
  • Male
  • Nicotinamide Phosphoribosyltransferase / metabolism*
  • PPAR gamma / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Sterol Regulatory Element Binding Proteins / metabolism


  • Cytokines
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • PPAR gamma
  • RNA, Messenger
  • Srebf2 protein, rat
  • Sterol Regulatory Element Binding Proteins
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, rat
  • Glucose