Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans
| Autor: | C Bogardus, David M. Mott, B. L. Nyomba, Y Kida |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty medicine.medical_treatment Stimulation Biology chemistry.chemical_compound Insulin resistance Internal medicine Cyclic AMP medicine Humans Insulin Cyclic adenosine monophosphate Protein kinase A Glycogen synthase Protein Kinase Inhibitors Muscles Racial Groups Skeletal muscle General Medicine medicine.disease Glycogen Synthase Endocrinology medicine.anatomical_structure chemistry Glycogenesis biology.protein Female Insulin Resistance Research Article |
| Zdroj: | Journal of Clinical Investigation. 87:673-679 |
| ISSN: | 0021-9738 |
| DOI: | 10.1172/jci115045 |
| Popis: | Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resistant subjects (group R). Muscle biopsies were obtained from quadriceps femoris muscle at times 0, 10, 20, 40, and 120 min. Insulin infusion resulted in significant inhibition of A-kinase activity at 20 and/or 40 min using 0.2, 0.6, and 1.0 microM cyclic AMP in group S. A-kinase activities both before and after insulin administration were lower in group S than in group R using 0.6 microM cyclic AMP. The decrease in apparent affinity for cyclic AMP during insulin infusion was larger for group S compared with group R. Glycogen synthase activity increased significantly after insulin infusion in both groups and was higher in group S compared with group R. The data suggest that a defective response of A-kinase to insulin in insulin-resistant subjects could contribute to their reduced insulin stimulation of skeletal muscle glycogen synthase. |
| Databáze: | OpenAIRE |
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