Abstract
The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of approximately 10 nM and total inhibition at 1 microM. This concentration of wortmannin also decreased the contraction-stimulated glucose transport and uptake by approximately 30-70% without confounding effects on contractility or on muscle ATP and phosphocreatine concentrations. At higher concentrations (3 and 10 microM), wortmannin completely blocked the contraction-stimulated glucose uptake but also decreased the contractility. In conclusion, inhibition of PI 3-kinase with wortmannin in skeletal muscle coincides with inhibition of insulin-stimulated glucose uptake and transport. Furthermore, in contrast to recent findings in incubated muscle, wortmannin also inhibited contraction-stimulated glucose uptake and transport. The inhibitory effect of wortmannin on contraction-stimulated glucose uptake may be independent of PI 3-kinase activity or due to inhibition of a subfraction of PI 3-kinase with low sensitivity to wortmannin.
| Original language | English |
|---|---|
| Journal | Journal of Applied Physiology |
| Volume | 81 |
| Issue number | 4 |
| Pages (from-to) | 1501-1509 |
| Number of pages | 9 |
| ISSN | 8750-7587 |
| Publication status | Published - 1996 |
Keywords
- 1-Phosphatidylinositol 4-Kinase
- Adenosine Triphosphate
- Androstadienes
- Animals
- Electric Stimulation
- Glucose
- Hindlimb
- Hypoglycemic Agents
- Insulin Antagonists
- Male
- Membranes
- Muscle Contraction
- Muscle, Skeletal
- Oxygen Consumption
- Phosphocreatine
- Phosphorylation
- Phosphotransferases (Alcohol Group Acceptor)
- Rats
- Rats, Wistar
- Receptor, Insulin