Effects of genistein on insulin pathway related genes in mouse differentiated myoblast C2C12 cell line: evidences for two independent modes of action

Sławomir Lewicki, Aneta Lewicka, Bolesław Kalicki, Agnieszka Sobolewska-Ruta, Bogdan Debski, Robert Zdanowski, Tomasz Syryło, Malgorzata Kloc, Jacek Zbigniew Kubiak

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

INTRODUCTION: Genistein (plant isoflavone) is a well-known anti-cancer drug with estrogenic-like properties. Genistein also regulates sugar and lipid metabolism; thus, it has anti-diabetic properties. The aim of the study was to evaluate in vitro effects of genistein on glucose transport, fatty acids oxidation, activation of PKB, and expression of genes related to insulin pathway in differentiated myoblast C2C12 mouse cell line.

MATERIAL AND METHODS: Differentiated myoblast C2C12 mouse cell line was used to assess the effects of different genistein concentrations on glucose transport and fatty acids oxidation measured by radioactivity technique, activation of PKB, and expression of selected genes related to insulin signaling pathway (IR-α, IR-β, IRS-1, PKB, GLUT-4, PP2A, SH-PTP2) at the mRNA and protein levels. Cells were incubated with various concentrations of genistein under standard conditions for 0-48 hours.

RESULTS: Genistein in low concentrations (0.1-1 µM) significantly increased glucose transport and decreased fatty acids oxidation in C2C12 cells after 48 h of incubation. High concentration of genistein (50 µM) had the opposite effect. Genistein stimulated PKB phosphorylation during the first 5-10 minutes of incubation. There was no significant impact on the protein expression of selected genes (IR-α, IR-β, IRS-1, PKB, GLUT-4, PP2A-Cα, ER-α and ER-β) after 48 h treatment. We observed inverse correlation between genistein concentration and the expression of SH-PTP2 protein. Genistein affected the expression pattern of mRNAs for genes related to the insulin pathway; however, not the expression of the encoded proteins.

CONCLUSIONS: The results of this study showed that depending on the concentration and time of incubation genistein significantly affects glucose and lipid metabolism and at low concentration modifies expression pattern of a few genes in C2C12 cells.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalFolia Histochemica et Cytobiologica
Volume56
Issue number3
Early online dateJul 12 2018
DOIs
StatePublished - Sep 24 2018

Keywords

  • Journal Article
  • C2C12 cell line
  • Genistein
  • Insulin pathway proteins
  • Glucose transport
  • Fatty acids oxidation
  • Cell Line
  • Phosphorylation
  • Genistein/metabolism
  • Proto-Oncogene Proteins c-akt/metabolism
  • Signal Transduction/drug effects
  • Animals
  • Myoblasts/cytology
  • Cell Differentiation/physiology
  • Lipid Metabolism/physiology
  • Insulin/metabolism
  • Glucose/metabolism
  • Mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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