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

Qin Sun, Ling Li, Renzhe Li, Mengliu Yang, Hua Liu, Michael J. Nowicki, Haihong Zong, Jun Xu, Gangyi Yang

Research output: Contribution to journalArticle

44 Citations (Scopus)

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. 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- (PPAR) 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 PPAR and SREBP-2.

Original languageEnglish (US)
Pages (from-to)311-320
Number of pages10
JournalAnnals of Medicine
Volume41
Issue number4
DOIs
StatePublished - 2009

Fingerprint

Nicotinamide Phosphoribosyltransferase
Insulin Resistance
Lipids
Sterol Regulatory Element Binding Protein 2
Insulin Receptor Substrate Proteins
Peroxisome Proliferator-Activated Receptors
Glucose Clamp Technique
Tyrosine
Adipose Tissue
Plasmids
Phosphorylation
Insulin
Messenger RNA
Injections
Liver
High Fat Diet
Lipid Metabolism
Proteins
Up-Regulation
Hormones

Keywords

  • Insulin sensitivity
  • Lipid metabolism
  • PPAR
  • SREBP-2
  • Visfatin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats. / Sun, Qin; Li, Ling; Li, Renzhe; Yang, Mengliu; Liu, Hua; Nowicki, Michael J.; Zong, Haihong; Xu, Jun; Yang, Gangyi.

In: Annals of Medicine, Vol. 41, No. 4, 2009, p. 311-320.

Research output: Contribution to journalArticle

Sun, Qin ; Li, Ling ; Li, Renzhe ; Yang, Mengliu ; Liu, Hua ; Nowicki, Michael J. ; Zong, Haihong ; Xu, Jun ; Yang, Gangyi. / Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats. In: Annals of Medicine. 2009 ; Vol. 41, No. 4. pp. 311-320.
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T1 - Overexpression of visfatin/PBEF/Nampt alters whole-body insulin sensitivity and lipid profile in rats

AU - Sun, Qin

AU - Li, Ling

AU - Li, Renzhe

AU - Yang, Mengliu

AU - Liu, Hua

AU - Nowicki, Michael J.

AU - Zong, Haihong

AU - Xu, Jun

AU - Yang, Gangyi

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N2 - 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- (PPAR) 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 PPAR and SREBP-2.

AB - 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- (PPAR) 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 PPAR and SREBP-2.

KW - Insulin sensitivity

KW - Lipid metabolism

KW - PPAR

KW - SREBP-2

KW - Visfatin

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