Impaired activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 in cultured preadipocyte-derived adipocytes and myotubes of obese subjects.

Details

Serval ID
serval:BIB_63916FC1A1EE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Impaired activation of protein kinase C-zeta by insulin and phosphatidylinositol-3,4,5-(PO4)3 in cultured preadipocyte-derived adipocytes and myotubes of obese subjects.
Journal
The Journal of clinical endocrinology and metabolism
Author(s)
Sajan M.P., Standaert M.L., Miura A., Bandyopadhyay G., Vollenweider P., Franklin D.M., Lea-Currie R., Farese R.V.
ISSN
0021-972X
Publication state
Published
Issued date
2004
Peer-reviewed
Oui
Volume
89
Number
8
Pages
3994-8
Language
english
Notes
Publication types: Journal Article - Publication Status: ppublish
Abstract
Insulin resistance in obesity is partly due to diminished glucose transport in myocytes and adipocytes, but underlying mechanisms are uncertain. Insulin-stimulated glucose transport requires activation of phosphatidylinositol (PI) 3-kinase (3K), operating downstream of insulin receptor substrate-1. PI3K stimulates glucose transport through increases in PI-3,4,5-(PO(4))(3) (PIP(3)), which activates atypical protein kinase C (aPKC) and protein kinase B (PKB/Akt). However, previous studies suggest that activation of aPKC, but not PKB, is impaired in intact muscles and cultured myocytes of obese subjects. Presently, we examined insulin activation of glucose transport and signaling factors in cultured adipocytes derived from preadipocytes harvested during elective liposuction in lean and obese women. Relative to adipocytes of lean women, insulin-stimulated [(3)H]2-deoxyglucose uptake and activation of insulin receptor substrate-1/PI3K and aPKCs, but not PKB, were diminished in adipocytes of obese women. Additionally, the direct activation of aPKCs by PIP(3) in vitro was diminished in aPKCs isolated from adipocytes of obese women. Similar impairment in aPKC activation by PIP(3) was observed in cultured myocytes of obese glucose-intolerant subjects. These findings suggest the presence of defects in PI3K and aPKC activation that persist in cultured cells and limit insulin-stimulated glucose transport in adipocytes and myocytes of obese subjects.
Keywords
1-Phosphatidylinositol 3-Kinase, Adipocytes, Adult, Cells, Cultured, Deoxyglucose, Enzyme Activation, Female, Humans, Insulin, Insulin Receptor Substrate Proteins, Middle Aged, Muscle Fibers, Skeletal, Obesity, Phosphatidylinositol Phosphates, Phosphoproteins, Phosphorylation, Protein Kinase C, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Stem Cells
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:06
Last modification date
20/08/2019 14:20
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