| Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in hepatic cells. | |
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MedLine Citation:
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PMID: 19817973 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Low levels of melatonin in circulation had been reported to be related to the development of diabetes. Melatonin administration in animals increases hepatic glycogen content to lower blood glucose. However, the signaling pathway for these effects is still unclear. The present study shows that intraperitoneal injection of 10 mg/kg melatonin ameliorated glucose utilization and insulin sensitivity in high fat diet-induced diabetic mice with an increase in hepatic glycogen and improvement in liver steatosis. We used HepG2 cells to investigate the signaling pathways for the melatonin-stimulated hepatic glycogen increment. Treatment of HepG2 cells with 1 nm melatonin markedly increased glycogen synthesis which was blocked by the melatonin receptor antagonist luzindole. In addition, melatonin increased the phosphorylation of subcellular signals at the level of protein kinase C zeta (PKCzeta), Akt, and glycogen synthase kinase 3beta (GSK3beta) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCzeta pseudo-peptide. However, 3',5'-cyclic adenosine monophosphate-activated protein kinase (AMPK) was not influenced by melatonin treatment. Taken together, melatonin improves glucose intolerance and insulin resistance in high fat diet-induced diabetic mice and stimulates glycogen synthesis via a PKCzeta-Akt-GSK3beta pathway in HepG2 cells. |
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Authors:
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Jiunn-Min Shieh; Hung-Tsung Wu; Kai-Chun Cheng; Juei-Tang Cheng |
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Publication Detail:
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Type: Journal Article Date: 2009-10-10 |
Journal Detail:
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Title: Journal of pineal research Volume: 47 ISSN: 1600-079X ISO Abbreviation: J. Pineal Res. Publication Date: 2009 Nov |
Date Detail:
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Created Date: 2009-10-16 Completed Date: 2010-01-08 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 339-44 Citation Subset: IM |
Affiliation:
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Department of Chest Medicine, Chi-Mei Medical Center, Yong Kang City, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antioxidants / pharmacology Blotting, Western Cell Line, Tumor Diabetes Mellitus, Experimental / etiology* Dietary Fats / adverse effects* Fatty Liver / drug therapy Glycogen / biosynthesis*, metabolism Glycogen Synthase Kinase 3 / metabolism* Male Melatonin / pharmacology* Mice Mice, Inbred C57BL Phosphorylation / drug effects Protein Kinase C / metabolism* Proto-Oncogene Proteins c-akt / metabolism* Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Dietary Fats; 73-31-4/Melatonin; 9005-79-2/Glycogen; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.1/protein kinase C zeta; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.26/Glycogen Synthase Kinase 3 |
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