Abstract
Some of inositol derivatives have been reported to help the action of insulin stimulating glucose uptake in skeletal muscle cells. Rat L6 myotubes were employed in an attempt to develop an in vitro model system for investigation of the possible insulin-like effect of eight inositol derivatives, namely allo-inositol, d-chiro-inositol l-chiro-inositol, epi-inositol, muco-inositol, myo-inositol, scyllo-inositol and d-pinitol. At a higher concentration of 1 mM seven inositol derivatives other than myo-inositol were able to stimulate glucose uptake, while at 0.1 mM only d-chiro-inositol, l-chiro-inositol, epi-inositol and muco-inositol could induce glucose uptake, indicating their significant insulin-mimetic activity. Immunoblot analyses revealed that at least d-chiro-inositol, l-chiro-inositol, epi-inositol, muco-inositol and d-pinitol were able to induce translocation of glucose transporter 4 (GLUT4) to plasma membrane not only in L6 myotubes but also in skeletal muscles of rats ex vivo. These results demonstrated that L6 myotubes appeared efficient as an in vitro system to identify inositol derivatives exerting an insulin-like effect on muscle cells depending on the induced translocation of GLUT4.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- 2DG:
-
[1,2-3H(N)] 2-Deoxy-d-glucose
- GLUT4:
-
Glucose transporter 4
- IRβ:
-
Insulin receptor β-subunit
- KRH:
-
Krebs-Ringer HEPES
References
Bates SH, Jones RB, Bailey CJ (2000) Insulin-like effect of pinitol. Br J Pharmacol 130:1944–1948
Benjamin J, Agam G, Levine J, Bersudsky Y, Kofman O, Belmaker RH (1995) Inositol treatment in psychiatry. Psychopharmacol Bull 31:167–175
Iuorno MJ, Jakubowicz DJ, Baillargeon JP, Dillon P, Gunn RD, Allan G, Nestler JE (2002) Effects of D-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 8:417–423
Kawa JM, Taylor CG, Przybylski R (2003) Buckwheat concentrate reduces serum glucose in streptozotoxin-diabetic rats. J Agric Food Chem 51:7287–7291
Khan AH, Pessin JE (2002) Insulin regulation of glucose uptake: a complex interplay of intracellular signaling pathways. Diabetologia 45:1475–1483
Klip A, Ishiki M (2005) Recent developments in the regulation of glucose transporter-4 traffic: new signals, locations, and partners. Endocrinology 146:5071–5078
McLaurin J, Golomb R, Jurewicz A, Antel JP, Fraser PE (2000) Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta-induced toxicity. J Biol Chem 275:18495–18502
Nedachi T, Kanzaki M (2006) Regulation of glucose transporters by insulin and extracellular glucose in C2C12 myotubes. Am J Physiol Endocrinol Metab 291:E817–E828
Nishiumi S, Ashida H (2007) Rapid preparation of a plasma membrane fraction from adipocytes and muscle cells: application to detection of translocated glucose transporter 4 on the plasma membrane. Biosci Biotechnol Biochem 71:2343–2346
Ortmeyer HK, Huang LC, Zhang L, Hansen BC, Larner J (1993) Chiroinositol deficiency and insulin resistance. II. Acute effects of D-chiroinositol administration in streptozotocin-diabetic rats, normal rats given a glucose load, and spontaneously insulin-resistant rhesus monkeys. Endocrinology 132:646–651
Ostlund RE, Sherman WR (1998) Pinitol and derivatives thereof for the treatment of metabolic disorders. US Patent 5,827,896, 27 Oct 1998
Petersen KF, Shulman GI (2006) Etiology of insulin resistance. Am J Med 119:10S–16S
Sarabia V, Ramlal T, Klip A (1990) Glucose uptake in human and animal muscle cells in culture. Biochem Cell Biol 68:536–542
Weeks CE, Albany N (2003) Stimulating transport of glucose into animal tissue by the administration of pinitol. US Patent 6,518,318 B1, 11 Feb 2003
Acknowledgments
We thank M. Yamaguchi, Hokko Chemical Industry Co., Ltd, and T. Yoshida, Fujicco Co., Ltd, for some of the inositol derivatives and generous supports. This work was supported in part by Fermentation and Metabolism Research Grant Awards from Japan Bioindustry Association to KY (2006).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yap, A., Nishiumi, S., Yoshida, Ki. et al. Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives. Cytotechnology 55, 103–108 (2007). https://doi.org/10.1007/s10616-007-9107-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-007-9107-y