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- Title
PKC-zeta mediates insulin effects on glucose transport in cultured preadipocyte-derived human adipocytes.
- Authors
Bandyopadhyay, Gautam; Sajan, Mini P; Kanoh, Yoshinori; Standaert, Mary L; Quon, Michael J; Lea-Currie, Rene; Sen, Anindita; Farese, Robert V
- Abstract
Insulin-stimulated glucose transport is impaired in the early phases of type 2 diabetes mellitus. Studies in rodent cells suggest that atypical PKC (aPKC) isoforms (zeta, lamda, and iota) and PKB, and their upstream activators, PI3K and 3-phosphoinositide-dependent protein kinase-1 (PDK-1), play important roles in insulin-stimulated glucose transport. However, there is no information on requirements for aPKCs, PKB, or PDK-1 during insulin action in human cell types. Presently, by using preadipocyte-derived adipocytes, we were able to employ adenoviral gene transfer methods to critically examine these requirements in a human cell type. These adipocytes were found to contain PKC-zeta, rather than PKC-lamda/iota, as their major aPKC. Expression of kinase-inactive forms of PDK-1, PKC-zeta, and PKC-lamda (which functions interchangeably with PKC-zeta) as well as chemical inhibitors of PI 3-kinase and PKC-zeta/lamda, wortmannin and the cell-permeable myristoylated PKC-zeta pseudosubstrate, respectively, effectively inhibited insulin-stimulated glucose transport. In contrast, expression of a kinase-inactive, activation-resistant, triple alanine mutant form of PKB-alpha had little or no effect, and expression of wild-type and constitutively active PKC-zeta or PKC-lamda increased glucose transport. Our findings provide convincing evidence that aPKCs and upstream activators, PI 3-kinase and PDK-1, play important roles in insulin-stimulated glucose transport in preadipocyte-derived human adipocytes.
- Subjects
GLUCOSE metabolism; ANIMAL experimentation; BIOLOGICAL transport; CELL lines; CELLS; COMPARATIVE studies; FAT cells; INSULIN; RESEARCH methodology; MEDICAL cooperation; MICE; RESEARCH; RESEARCH funding; STEM cells; TRANSFERASES; EVALUATION research; SKELETAL muscle
- Publication
Journal of Clinical Endocrinology & Metabolism, 2002, Vol 87, Issue 2, p716
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jcem.87.2.8252