Abstract
Using siRNA-mediated gene silencing in cultured adipocytes, we have dissected the insulin-signalling pathway leading to translocation of GLUT4 glucose transporters to the plasma membrane. RNAi (RNA interference)-based depletion of components in the putative TC10 pathway (CAP, CrkII and c-Cbl plus Cbl-b) or the phospholipase Cγ pathway failed to diminish insulin signalling to GLUT4. Within the phosphoinositide 3-kinase pathway, loss of the 5′-phosphatidylinositol 3,4,5-trisphosphate phosphatase SHIP2 was also without effect, whereas depletion of the 3′-phosphatase PTEN significantly enhanced insulin action. Downstream of phosphatidylinositol 3,4,5-trisphosphate and PDK1, silencing the genes encoding the protein kinases Akt1/PKBα, or CISK(SGK3) or protein kinases Cλ/ζ had little or no effect, but loss of Akt2/PKBβ significantly attenuated GLUT4 regulation by insulin. These results show that Akt2/PKBβ is the key downstream intermediate within the phosphoinositide 3-kinase pathway linked to insulin action on GLUT4 in cultured adipocytes, whereas PTEN is a potent negative regulator of this pathway.
Original language | English (US) |
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Pages (from-to) | 817-821 |
Number of pages | 5 |
Journal | Biochemical Society transactions |
Volume | 32 |
Issue number | 5 |
DOIs | |
State | Published - Nov 2004 |
Externally published | Yes |
Keywords
- Gene silencing
- Glucose
- Insulin signalling
- Phosphoinositide 3-kinase (PI3K)
- Phospholipase Cγ
- Protien kinase Cλ/ζ siRNA
ASJC Scopus subject areas
- Biochemistry