title: Melatonin stimulates glucose transport via insulin receptor substrate-1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells.
abstract: The prevalence of diabetes has exponentially increased in recent decades due to environmental factors such as nocturnal lifestyle and aging, both of which influence the amount of melatonin produced in the pineal gland. The present study investigated the effect of melatonin on signaling pathways of glucose transport in C2C12 mouse skeletal muscle cells. Intriguingly, treatment of C2C12 cells with melatonin (1 nm) stimulated glucose uptake twofold increase. Melatonin-stimulated glucose transport was inhibited with co-treatment with the melatonin receptor antagonist luzindole. Furthermore, treatment of stably over-expressed melatonin receptor type 2B containing C2C12 myotubes with melatonin amplified glucose transport c. 13-fold. Melatonin also increased the phosphorylation level of insulin receptor substrate-1 (IRS-1) and the activity of phosphoinositide 3-kinase (PI-3-kinase). However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK), another important glucose transport stimulatory mediator via an insulin-independent pathway, was not influenced by melatonin treatment. Activity of p38 mitogen-activated protein kinase (MAPK), a downstream mediator of AMPK, was also not changed by melatonin. In addition, melatonin increased the expression level of forkhead box A2, which was recently discovered to regulate fatty acid oxidation and to be inhibited by insulin. In summary, melatonin stimulates glucose transport to skeletal muscle cells via IRS-1/PI-3-kinase pathway, which implies, at the molecular level, its role in glucose homeostasis and possibly in diabetes. Additionally, exposure to light at night and aging, both of which lower endogenous melatonin levels may contribute to the incidence and/or development of diabetes.
authors.affiliation: Department of Biochemisty and Molecular Biology, College of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Ha
authors.forename: Sung-Vin
authors.initials: SV
authors.lastname: Yim
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Cho
authors.forename: Hyung Hwan
authors.initials: HH
authors.lastname: Baik
mesh_terms: D001692:Biological Transport; D015153:Blotting, Western; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins; D008550:Melatonin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*
chemical_list: D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D019869:Phosphatidylinositol 3-Kinases; D005947:Glucose; D008550:Melatonin