Melatonin stimulates glucose transport via insulin receptor substrate‐1/phosphatidylinositol 3‐kinase pathway in C2C12 murine skeletal muscle cells
Abstract
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 C 2 C 12 mouse skeletal muscle cells. Intriguingly, treatment of C 2 C 12 cells with melatonin (1 n m) 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 C 2 C 12 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.
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Melatonin is an internal indoleamine hormone that participates in different physiologic procedures and is regulated through the hypothalamic suprachiasmatic nucleus (SCN).
“Melatonin (N-acetyl-5-methoxytryptamine) as an internal indoleamine hormone takes part in different physiologic procedures and is regulated through the hypothalamic suprachiasmatic nucleus (SCN).”
Melatonin prevents insulin resistance by activating the cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB)-peroxisome proliferator-activated receptor gamma coactivator 1-(PGC-1α) pathway.
“Furthermore, melatonin prevents insulin resistance by activating the cyclic adenosine monophosphate (cAMP)response element binding protein (CREB)-peroxisome proliferator-activated receptor gamma coactivator 1-(PGC-1α) pathway. 9”
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“9 It also provokes the IRS1-PI3K-PKC route to improve glucose absorption in skeletal muscle.”
- Authors
- Ha, E., Yim, S., Chung, J., Yoon, K., Kang, I., Cho, Y. H., & Baik, H. H.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Baik, Hyung Hwan
- Venue
- Journal of Pineal Research
- Publisher
- Wiley
- Published
- 2006-06-28
- Volume
- 41
- Issue
- 1
- Pages
- 67-72
- ISSN
- 0742-3098 (ISSN-L)
- 1600-079X
- OpenAlex
- W2085663109
- Cited by
- 124
- References
- 37
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 6 · 2018: 10 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 7 · 2013: 13 · 2012: 8
- FWCI
- 1.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pineal Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Keywords
- melatonin, glucose transport, IRS-1, phosphatidylinositol 3-kinase, skeletal muscle, C2C12 myotubes, luzindole, AMPK, p38 MAPK, glucose homeostasis, diabetes mellitus, light at night, aging
- MeSH terms
- Biological Transport, Cell Line, Glucose, Melatonin, Phosphoproteins, Blotting, Western, Muscle, Skeletal, Phosphatidylinositol 3-Kinases, Insulin Receptor Substrate Proteins
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