2006 Fiscal Year Final Research Report Summary
The Pathophysiological Role of Protein Phosphatase 2A (PP2A) in metabolic Syndrome
| Project/Area Number |
17590927
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | Shiga University of Medical Science |
|---|
Principal Investigator |
UGI Satoshi Shiga University of Medical Science, Assistant Professor, 医学部, 助手 (20378483)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MAEGAWA Hiroshi Shiga University of Medical Science, Associate Professor, 医学部, 助教授 (00209363)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Keywords | diabetes mellitus / insulin resistance / phosphatase / free fatty acid |
|---|
| Research Abstract |
We have found that preincubation of palmitate and C2-ceramide induced insulin resistance through inhibiting Akt in 3T3-L1 adipocytes. The inhibitory effect of palmitate was blocked by. myriocin, ceramide synthesis inhibitor. Myristate or oleate, which are not the precursor of ceramide, did not cause insulin resistance. We also found that PP2A activity was stimulated by palmitate and okadaic acid, PP2A inhibitor, blocked palmitate-induced Akt inhibition. These results suggest that palmitate inhibits Akt through activating Akt by de novo synthesis of ceramide in the cells in adipocytes.
On the other hand, although, palmitate and C2-ceramide inhibited Akt in Fao rat hepatoma cells as same as in 3T3-L1 adipocytes, the inhibition was not accompanied by PP2A activation. In support of this result, okadaic acid or myriocin did not block palmitate-induced Akt inhibition. These results suggest that either PP2A activation or ceramide synthesis is not involved in palmitate-induced insulin resistance in Fao cells.
Finally, in L6 myocytes, palmitate and C2-ceramide induced Akt inhibition was partially blocked okadaic acid. Myristate did not inhibit Akt and myriocin partially blocked palmitate' s effect. In conclusion, palmitate causes insulin resistance through different mechanisms among different cell types
|
