Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity
| Autor: | S. I. Itani, Walter J. Pories, Kenneth G. MacDonald, G. L. Dohm, Qian Zhou |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Fatty Acids Nonesterified Receptor tyrosine kinase Body Mass Index Insulin resistance Thinness Reference Values Internal medicine Internal Medicine medicine Humans Insulin Obesity Kinase activity Muscle Skeletal Protein Kinase C Protein kinase C Insulin-like growth factor 1 receptor biology Cell Membrane Skeletal muscle Alkaline Phosphatase medicine.disease Receptor Insulin Isoenzymes Insulin receptor medicine.anatomical_structure Endocrinology biology.protein Female Insulin Resistance |
| Zdroj: | Diabetes. 49:1353-1358 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.49.8.1353 |
| Popis: | This study was conducted to investigate the possible involvement of protein kinase C (PKC) and serine/threonine phosphorylation of the insulin receptor in insulin resistance and/or obesity. Insulin receptor tyrosine kinase activity was depressed in muscle from obese insulin-resistant patients compared with lean insulin-responsive control subjects. Alkaline phosphatase treatment resulted in a significant 48% increase in in vitro insulin-stimulated receptor tyrosine kinase activity in obese but not lean muscle. To investigate the involvement of PKC in skeletal muscle insulin resistance and/or obesity, membrane-associated PKC activity and the protein content of various PKC isoforms were measured in human skeletal muscle from lean, insulin-responsive, and obese insulin-resistant patients. Membrane-associated PKC activity was not changed; however, PKC-beta protein content, assayed by Western blot analysis, was significantly higher, whereas PKC-theta, -eta, and -mu were significantly lower in muscle from obese patients compared with muscle from lean control subjects. Incubation of muscle strips with insulin significantly increased membrane-associated PKC activity in muscle from obese but not lean subjects. PKC-delta, -beta, and -theta were translocated from the cytosol to the membrane fraction in response to insulin treatment. These results suggest that in skeletal muscle from insulin-resistant obese patients, insulin receptor tyrosine kinase activity was reduced because of hyperphosphorylation on serine/threonine residues. Membrane-associated PKC-beta protein was elevated under basal conditions, and membrane-associated total PKC activity was increased under insulin-stimulated conditions in muscle from obese insulin-resistant patients. Thus, we postulate that the decreased tyrosine kinase activity of the insulin receptor may be caused by serine/threonine phosphorylation by PKC. |
| Databáze: | OpenAIRE |
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