title: Betel nut extract and arecoline block insulin signaling and lipid storage in 3T3-L1 adipocytes.
abstract: 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.
authors.affiliation: Department of Medical Genetics, College of Medicine, Kaohsiung Medical University, Taiwan, Republic of China.
authors.forename: Tusty-Jiuan
authors.initials: TJ
authors.lastname: Hsieh
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Hsieh
authors.forename: Ming-Tsang
authors.initials: MT
authors.lastname: Wu
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
authors.forename: Pi-Jung
authors.initials: PJ
authors.lastname: Hsiao
authors.forename: Kun-Der
authors.initials: KD
authors.lastname: Lin
authors.forename: Pong-Chun
authors.initials: PC
authors.lastname: Chou
authors.forename: Shyi-Jang
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001114:Areca / Q000009:adverse effects* / Q000737:chemistry; D001115:Arecoline / Q000009:adverse effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D055504:Insulin Receptor Substrate Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D000070778:Perilipin-1; D000070780:Perilipin-2; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002352:Carrier Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D008565:Membrane Proteins; D000070778:Perilipin-1; D000070780:Perilipin-2; D010750:Phosphoproteins; D010936:Plant Extracts; C000602983:Plin2 protein, mouse; D001115:Arecoline; D064429:Fatty Acid Synthases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose