Functional Role of Neuroendocrine-Specific Protein-Like 1 in Membrane Translocation of GLUT4
- Takaaki Ikemoto1,
- Takamitsu Hosoya2,
- Kumi Takata1,
- Hiroshi Aoyama3,
- Toshiyuki Hiramatsu2,
- Hirotaka Onoe1,
- Masaaki Suzuki4 and
- Makoto Endo5
- 1Functional Probe Research Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan;
- 2Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology and SORST (Solution Oriented Research for Science and Technology), Japan Science and Technology Agency, Yokohama, Japan;
- 3Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan;
- 4Molecular Imaging Medicinal Chemistry Laboratory, RIKEN Center for Molecular Imaging Science, Kobe, Japan;
- 5Faculty of Health and Medical Care, Saitama Medical University, Saitama, Japan.
- Corresponding author: Functional Probe Research Laboratory, tikemotoriko{at}riken.jp.
Abstract
OBJECTIVE In skeletal muscles, dantrolene inhibits the exercise-induced membrane translocation of GLUT4. It has been postulated that the inhibitory action of dantrolene on Ca2+ release from the sarcoplasmic reticulum (SR) causes inhibition of exercise-induced glucose uptake; however, the precise mechanism has not been adequately studied.
RESEARCH DESIGN AND METHODS We discovered that dantrolene can bind to skeletal-type neuroendocrine-specific protein-like 1 (sk-NSPl1) with photoreactive dantrolene 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 both isolated and in situ skeletal muscles after electrical stimulation using our mutant mouse.
RESULTS In sk-NSPl1–deficient muscles, exercise-induced glucose uptake was totally abolished with no change in insulin-induced glucose uptake. The Ca2+ release mechanism and its inhibition by dantrolene 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 hind limbs, but that in mutant mice was unchanged.
CONCLUSIONS sk-NSPl1 is a novel dantrolene 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.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received May 19, 2009.
- Accepted August 17, 2009.
- © 2009 American Diabetes Association
