| Title | Functional role of NSP-like 1 protein in membrane translocation of glucose transporter 4. | | Author(s) | Ikemoto T, Hosoya T, Takata K, Aoyama H, Hiramatsu T, Onoe H, Suzuki M, Endo M | | Institution | Functional Probe Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe 650-0047, Japan. | | Source | Diabetes 2009 Aug 31. | | Abstract | Objective- In skeletal muscles, dantrolene (Dan) inhibits the exercise-induced membrane translocation of glucose transporter 4 (GLUT4). It has been postulated that the inhibitory action of Dan on Ca(2+) release from the sarcoplasmic reticulum (SR) causes the inhibition of exercise-induced glucose uptake (EIGU); however, the precise mechanism has not been adequately studied. Research design and methods- We discovered that Dan can bind to skeletal-type neuroendocrine-specific protein like 1 (sk-NSPl1) with photo-reactive Dan derivatives. In sk-NSPl1-deficient muscles, we examined the change in glucose uptake and the membrane translocation of GLUT4. In addition, we examined the change in blood glucose and also measured the glycogen level in isolated and in situ skeletal muscles after electrical stimulation using our mutant mouse. Results- In sk-NSPl1-deficient muscles, EIGU was totally abolished with no change in insulin-induced glucose uptake. The Ca(2+) release mechanism and its inhibition by Dan were completely preserved in these muscles. The expression of GLUT4 in the mutant muscles also appeared unchanged. Confocal imaging and results using the membrane isolation method showed that exercise/contraction did not enhance GLUT4 translocation in these sk-NSPl1-deficient muscles under conditions of adequate muscle glycogen consumption. The blood glucose level in normal mice was reduced by electrical stimulation of the hindlimbs, but that in mutant mice was unchanged. Conclusions- Sk-NSPl1 is a novel Dan receptor that plays an important role in membrane translocation of GLUT4 induced by contraction/exercise. The 23 kDa sk-NSPl1 may also be involved in the regulation of glucose levels in the whole body. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19720795 |
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