Abstract
Certain PKC isoforms are stimulated by insulin and interact with IR as well as with IRS, but it is still not clear if specific PKC isoforms regulate IR signaling directly or through IRS-1. PKCα may regulate IRS activity in response to insulin. We investigated the possibility that PKCα may be important in insulin signaling. Studies were conducted on skeletal muscle in adult mice and on L6 skeletal cells. PKCα is constitutively associated with IRS-1, and insulin stimulation of PKCα causes disassociation of the two proteins within 5 min. Blockade of PKCα inhibited insulin-induced disassociation of PKCα from IRS1. Selective inhibition of PKCα increased the ability of insulin to reduce blood glucose levels. Insulin stimulation activates PKB and increases the association of PKCα with PKB. Blockade of PKCα increased threonine phosphorylation of PKB. We suggest that PKCα regulates insulin signaling in skeletal muscle through its disassociation from IRS-1 and association with PKB.
Original language | English |
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Pages (from-to) | 817-824 |
Number of pages | 8 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 345 |
Issue number | 2 |
DOIs | |
State | Published - 30 Jun 2006 |
Bibliographical note
Funding Information:This work was supported in part by Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, the Sorrell Foundation, and the Chief Scientist’s Office of the Israel Ministry of Health. S.R.S. is the incumbent of the Louis Fisher Chair in Cellular Pathology. This study represents an essential portion of the thesis submitted by M.C. in partial fulfillment of the requirements for the Ph. D. degree at Bar-llan University.
Funding
This work was supported in part by Russell Berrie Foundation and D-Cure, Diabetes Care in Israel, the Sorrell Foundation, and the Chief Scientist’s Office of the Israel Ministry of Health. S.R.S. is the incumbent of the Louis Fisher Chair in Cellular Pathology. This study represents an essential portion of the thesis submitted by M.C. in partial fulfillment of the requirements for the Ph. D. degree at Bar-llan University.
Funders | Funder number |
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Diabetes Care in Israel | |
Sorrell Foundation | |
Office of the Chief Scientist, Ministry of Health | |
Russell Berrie Nanotechnology Institute, Technion-Israel Institute of Technology |
Keywords
- Blood glucose
- IRS-1
- Insulin signaling
- PKB
- PKCα
- Serine phosphorylation
- Threonine phosphorylation