Back to Search
Start Over
A PPAR agonist improves TNF-alpha-induced insulin resistance of adipose tissue in mice.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2003 Sep 19; Vol. 309 (2), pp. 419-24. - Publication Year :
- 2003
-
Abstract
- Thiazolidinediones (TZDs), agonists for PPARs, have been shown to block the inhibitory effects of TNF-alpha on insulin action using cultured cells. In order to clarify the in vivo effects of TZDs on the inhibition of insulin sensitivity by TNF-alpha, insulin action in muscles and adipose tissues was assessed in the TNF-alpha-overexpression mice model using transplantation of cells secreting the TNF-alpha protein. After the pioglitazone treatment for 4 weeks, glucose uptake, insulin-induced IRS-1 phosphorylation, and lipoprotein lipase mRNA levels were analyzed. Pioglitazone did not ameliorate TNF-alpha-induced hyperinsulinemia in this model, as assessed by the OGTT. Glucose uptake and lipoprotein lipase mRNA levels were decreased by TNF-alpha in adipose tissues from the TNF-alpha-overexpressing mice, and pioglitazone blocked these inhibitions by TNF-alpha. On the other hand, in muscles, pioglitazone did not reverse the effects of TNF-alpha on insulin-induced phosphorylation of IRS-1, glucose uptake, and lipoprotein lipase mRNA levels. Present study revealed the different sensitivities of pioglitazone for the recovery of decreased insulin action in a TNF-alpha-overexpressing model using cell transplantation. These results suggest that the effect of TZDs is dependent on the fat distribution and accumulation in humans.
- Subjects :
- Animals
Blood Glucose analysis
Cells, Cultured
Glucose metabolism
Glucose Tolerance Test methods
Insulin blood
Insulin metabolism
Insulin Receptor Substrate Proteins
Lipoprotein Lipase genetics
Male
Mice
Mice, Inbred ICR
Mice, Nude
Muscle, Skeletal drug effects
Muscle, Skeletal metabolism
Phosphorylation drug effects
Pioglitazone
RNA, Messenger genetics
RNA, Messenger metabolism
Receptors, Cytoplasmic and Nuclear agonists
Transcription Factors agonists
Tumor Necrosis Factor-alpha genetics
Adipose Tissue drug effects
Adipose Tissue metabolism
Insulin Resistance
Lipoprotein Lipase metabolism
Phosphoproteins metabolism
Thiazoles pharmacology
Thiazolidinediones
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 309
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 12951066
- Full Text :
- https://doi.org/10.1016/j.bbrc.2003.07.007