Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes

Tusty Jiuan Hsieh, Pei Chen Hsieh, Ming Tsang Wu, Wei Chiao Chang, Pi Jung Hsiao, Kun Der Lin, Pong Chun Chou, Shyi Jang Shin

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


According to several population-based studies, betel nut chewing is associated with metabolic syndrome and diabetes in British South Asians and Taiwanese. However, the underlying molecular mechanism is not yet clear. Arecoline is an alkaloid-type natural product found in betel nuts. Our aim was to clarify the influence of betel nut extract and arecoline on lipid accumulation and insulin signaling in adipocytes. We found that betel nut extract and arecoline blocked lipid storage in 3T3-L1 adipocytes. The possible mechanism may function by inhibiting the expression of the insulin receptor, glucose transporter-4, fatty acid synthase, and the lipid droplet proteins perilipin and adipophilin. In addition, betel nut extract and arecoline increased the basal level of IRS-1 serine 307 phosphorylation and decreased insulin-stimulated IRS-1 tyrosine, Akt, and PI3 kinase phosphorylation. In conclusion, betel nut extract and arecoline have diabetogenic potential on adipocytes that may result in insulin resistance and diabetes at least in part via the obstruction of insulin signaling and the blockage of lipid storage.

Original languageEnglish
Pages (from-to)397-411
Number of pages15
JournalCell Biology and Toxicology
Issue number6
Publication statusPublished - Dec 2011
Externally publishedYes


  • Betel nut
  • Diabetes
  • IRS-1
  • Insulin resistance
  • Perilipin

ASJC Scopus subject areas

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis


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