Tissue-Specific Role of Glycogen Synthase Kinase 3β in Glucose Homeostasis and Insulin Action
| Autor: | Bradley W. Doble, Daniel J. Drucker, Satish Patel, Katrina MacAulay, Elaine M. Sinclair, James R. Woodgett |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
macromolecular substances AKT3 Cell Line MAP2K7 Glycogen Synthase Kinase 3 Mice chemistry.chemical_compound GSK-3 Internal medicine medicine Animals Homeostasis Insulin Muscle Skeletal Phosphorylase kinase Glycogen synthase Molecular Biology GSK3B Alleles Mice Knockout Glycogen Synthase Kinase 3 beta Glycogen biology Biological Transport Articles Cell Biology Mice Inbred C57BL Insulin receptor Glucose Endocrinology Liver chemistry Organ Specificity Gene Targeting biology.protein Gene Deletion Signal Transduction |
| Zdroj: | Molecular and Cellular Biology. 28:6314-6328 |
| ISSN: | 1098-5549 |
| DOI: | 10.1128/mcb.00763-08 |
| Popis: | Dysregulation of the protein kinase glycogen synthase kinase 3 (GSK-3) has been implicated in the development of type 2 diabetes mellitus. GSK-3 protein expression and kinase activity are elevated in diabetes, while selective GSK-3 inhibitors have shown promise as modulators of glucose metabolism and insulin sensitivity. There are two GSK-3 isoforms in mammals, GSK-3 and GSK-3. Mice engineered to lack GSK-3 die in late embryogenesis from liver apoptosis, whereas mice engineered to lack GSK-3 are viable and exhibit improved insulin sensitivity and hepatic glucose homeostasis. To assess the potential role of GSK-3 in insulin function, a conditional gene-targeting approach whereby mice in which expression of GSK-3 was specifically ablated within insulin-sensitive tissues were generated was undertaken. Liver-specific GSK-3 knockout mice are viable and glucose and insulin tolerant and display “normal” metabolic characteristics and insulin signaling. Mice lacking expression of GSK-3 in skeletal muscle are also viable but, in contrast to the liver-deleted animals, display improved glucose tolerance that is coupled with enhanced insulin-stimulated glycogen synthase regulation and glycogen deposition. These data indicate that there are not only distinct roles for GSK-3 and GSK-3 within the adult but also tissue-specific phenotypes associated with each of these isoforms. Glycogen synthase kinase 3 (GSK-3) is a highly conserved, ubiquitously expressed serine/threonine protein kinase that exists as two isoforms, GSK-3 (51 kDa) and GSK-3 (47 kDa), which are encoded by separate genes that produce highly ho |
| Databáze: | OpenAIRE |
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