Protein Kinase C-λ Knockout in Embryonic Stem Cells and Adipocytes Impairs Insulin-Stimulated Glucose Transport
| Autor: | Mini P. Sajan, Michael Leitges, Mary L. Standaert, Uschi Braun, Friederike Kruse, Yoshinori Kanoh, Robert V. Farese, Atsushi Miura, Gautam Bandyopadhyay |
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| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
Monosaccharide Transport Proteins medicine.medical_treatment Deoxyglucose Biology Mice Phosphatidylinositol 3-Kinases Endocrinology Adipocytes Phospholipase D medicine Animals Insulin Enzyme Inhibitors Protein kinase A Molecular Biology Cells Cultured Protein Kinase C Protein kinase C PI3K/AKT/mTOR pathway Mice Knockout Glucose Transporter Type 1 Stem Cells Glucose transporter Biological Transport Cell Differentiation General Medicine Protein-Tyrosine Kinases Embryo Mammalian Receptor Insulin Cell biology Enzyme Activation Isoenzymes Focal Adhesion Kinase 2 Glucose Mitogen-Activated Protein Kinases Signal transduction Signal Transduction |
| Zdroj: | Molecular Endocrinology. 18:373-383 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Atypical protein kinase C (aPKC) isoforms have been suggested to mediate insulin effects on glucose transport in adipocytes and other cells. To more rigorously test this hypothesis, we generated mouse embryonic stem (ES) cells and ES-derived adipocytes in which both aPKC-lambda alleles were knocked out by recombinant methods. Insulin activated PKC-lambda and stimulated glucose transport in wild-type (WT) PKC-lambda(+/+), but not in knockout PKC-lambda(-/-), ES cells. However, insulin-stimulated glucose transport was rescued by expression of WT PKC-lambda in PKC-lambda(-/-) ES cells. Surprisingly, insulin-induced increases in both PKC-lambda activity and glucose transport were dependent on activation of proline-rich tyrosine protein kinase 2, the ERK pathway, and phospholipase D (PLD) but were independent of phosphatidylinositol 3-kinase (PI3K) in PKC-lambda(+/+) ES cells. Interestingly, this dependency was completely reversed after differentiation of ES cells to adipocytes, i.e. insulin effects on PKC-lambda and glucose transport were dependent on PI3K, rather than proline-rich tyrosine protein kinase 2/ERK/PLD. As in ES cells, insulin effects on glucose transport were absent in PKC-lambda(-/-) adipocytes but were rescued by expression of WT PKC-lambda in these adipocytes. Our findings suggest that insulin activates aPKCs and glucose transport in ES cells by a newly recognized PI3K-independent ERK/PLD-dependent pathway and provide a compelling line of evidence suggesting that aPKCs are required for insulin-stimulated glucose transport, regardless of whether aPKCs are activated by PI3K-dependent or PI3K-independent mechanisms. |
| Databáze: | OpenAIRE |
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