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- Title
Effects of Conventional PKC (cPKC) Activation on Gene Expression in Adipocytes.
- Authors
Ikeda, Takahide; Kajita, Kazuo; Mori, Ichro; Matsubara, Keniji; Uno, Yoshihiro; Morita, Hiroyuki; Ishizuka, Tatsuo
- Abstract
Cytokine such as TNFα goes through activation of NF-κB and inhibits expression of PPARγin adipocyte. On the other hand, it is well known that phorbol ester-sensitive PKC, conventional PKC (cPKC), also activates NF-κB. Therefore, activation of cPKC may be possible to decrease the expression PPARγ and related genes. We examined to clarify the effects of activation of cPKC by tetradecanoyl phorbol ester (TPA) on the expression of adipocyte-specific genes in 3T3-L1 adipocytes. Since high glucose and insulin are able to activate cPKC, we evaluate the effects of these agonists on gene expression. PPARγ, aP2, lipoprotein lipase (LPL), fatty acid synthese (FAS) and adiponectin mRNA levels were measured with real time PCR. PKC activities were assessed with protein levels of PKC β and ε in the membrane fractions. Activities of NF-κB were assayed with commercially available kit. Each treatment with 100 nM TPA or 10 nM TNF α± for 24 hr decreased the PPARγmRNA levels to 52.2%, 25.6%, respectively in 3T3-L1 adipocytes. Levels of aP2, LPL, FAS and adiponectin mRNA concomitantly reduced. High glucose (15 mM), but not insulin (100nM), downregulated PPARγ, aP2, LPL and adiponectin mRNA levels to 73.3%, 66.5%, 43.1% and 63.6%, respectively. TNFα, TPA and high glucose increased NF-κB activity to 234%, 220% and 156%, respectively. These results indicated that cPKC regulates expression and activation of PPARγand related genes including aP2, LPL and adiponectin, probably via NF-κB. Moreover, it is suggested that cPKC activation induced with hyperglycemia may lead to insulin resistance due to reduced secretion of adiponectin. Recent researches have demonstrated that activation of cPKC attenuates insulin signaling via serine phosphorylation of IRS families. Our results indicated the other mechanism of insulin resistance caused by cPKC-induced attenuated adiponectin expression.
- Subjects
GENE expression; FAT cells; CYTOKINES; PROTEIN kinase C; BLOOD sugar; INSULIN; MESSENGER RNA
- Publication
Diabetes, 2007, Vol 56, pA355
- ISSN
0012-1797
- Publication type
Article