Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via a PKCζ-Akt-GSK3β pathway in hepatic cells

Jiunn Min Shieh, Hung Tsung Wu, Kai Chun Cheng, Juei Tang Cheng

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

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 ζ (PKCζ), Akt, and glycogen synthase kinase 3β (GSK3β) while the increase in glycogen synthesis induced by melatonin was inhibited by PKCζ 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 PKCζ-Akt-GSK3β pathway in HepG2 cells.

Original languageEnglish
Pages (from-to)339-344
Number of pages6
JournalJournal of Pineal Research
Volume47
Issue number4
DOIs
Publication statusPublished - Nov 1 2009
Externally publishedYes

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Keywords

  • Diabetes
  • Glycogen
  • Glycogen synthase kinase 3β
  • High fat diet
  • Insulin resistance
  • Melatonin
  • Protein kinase C ζ

ASJC Scopus subject areas

  • Endocrinology

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