| RRC ID |
42982
|
| Author |
Inada S, Ikeda Y, Suehiro T, Takata H, Osaki F, Arii K, Kumon Y, Hashimoto K.
|
| Title |
Glucose enhances protein tyrosine phosphatase 1B gene transcription in hepatocytes.
|
| Journal |
Mol Cell Endocrinol
|
| Abstract |
Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin receptor signal transduction pathway. We investigated the effects of glucose on PTP1B transcription in the human hepatocyte cell line Huh7. Using a reporter gene assay, we found that D-glucose dose-dependently enhanced the PTP1B promoter activity. Real-time PCR demonstrated that D-glucose also increased PTP1B mRNA expression. Protein kinase C (PKC) inhibitors partially but significantly inhibited the transactivation by D-glucose. Mithramycin, a Sp1 inhibitor, completely abrogated this transactivation. The deletion of three possible Sp1 sites in the promoter region of PTP1B significantly reduced the basal promoter activity and transactivation by D-glucose. Sp1 activation by PKC is one of the key mechanisms in the regulation of several gene expressions. Our data suggested that glucose enhanced PTP1B transcription through Sp1 activation by PKC. Increased hepatic PTP1B expression may partly explain glucose toxicity in diabetes.
|
| Volume |
271(1-2)
|
| Pages |
64-70
|
| Published |
2007-6-15
|
| DOI |
10.1016/j.mce.2007.04.005
|
| PII |
S0303-7207(07)00156-6
|
| PMID |
17509747
|
| MeSH |
Cell Line
Gene Expression Regulation*
Genes, Reporter
Glucose / metabolism*
Hepatocytes / cytology
Hepatocytes / physiology*
Humans
Insulin / metabolism
Plicamycin / metabolism
Promoter Regions, Genetic
Protein Kinase C / antagonists & inhibitors
Protein Synthesis Inhibitors / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 1
Protein Tyrosine Phosphatases / genetics
Protein Tyrosine Phosphatases / metabolism*
Signal Transduction / physiology
Sp1 Transcription Factor / metabolism
Transcription, Genetic*
|
| IF |
3.871
|
| Times Cited |
13
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
CELL BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
