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四氢大麻酚(THC)和一种亲脂性大麻提取物对正常及胰岛素抵抗的3T3-L1脂肪细胞的生物学效应。

Biological effects of THC and a lipophilic cannabis extract on normal and insulin resistant 3T3-L1 adipocytes.

作者信息

Gallant M, Odei-Addo F, Frost C L, Levendal R-A

机构信息

Department of Biochemistry & Microbiology, Nelson Mandela Metropolitan University, P.O. Box 77 000, Port Elizabeth 6031, South Africa.

出版信息

Phytomedicine. 2009 Oct;16(10):942-9. doi: 10.1016/j.phymed.2009.02.013. Epub 2009 Apr 2.

DOI:10.1016/j.phymed.2009.02.013
PMID:19345076
Abstract

Type 2 diabetes, a chronic disease, affects about 150 million people world wide. It is characterized by insulin resistance of peripheral tissues such as liver, skeletal muscle, and fat. Insulin resistance is associated with elevated levels of tumor necrosis factor alpha (TNF-alpha), which in turn inhibits insulin receptor tyrosine kinase autophosphorylation. It has been reported that cannabis is used in the treatment of diabetes. A few reports indicate that smoking cannabis can lower blood glucose in diabetics. Delta(9)-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. This study aimed to determine the effect of a lipophilic cannabis extract on adipogenesis, using 3T3-L1 cells, and to measure its effect on insulin sensitivity in insulin resistant adipocytes. Cells were cultured in Dulbecco's modified eagle medium (DMEM) with 10% fetal bovine serum (FBS) and differentiated over a 3 day period for all studies. In the adipogenesis studies, differentiated cells were exposed to the extract in the presence and absence of insulin. Lipid content and glucose uptake was subsequently measured. Insulin-induced glucose uptake increased, while the rate of adipogenesis decreased with increasing THC concentration. Insulin-resistance was induced using TNF-alpha, exposed to the extract and insulin-induced glucose uptake measured. Insulin-induced glucose was increased in these cells after exposure to the extract. Semiquantitative real time polymerase chain reaction (RT-PCR) was performed after ribonucleic acid (RNA) extraction to evaluate the effects of the extract on glucose transporter isotype 4 (GLUT-4), insulin receptor substrate-1 (IRS-1) and IRS-2 gene expression.

摘要

2型糖尿病是一种慢性疾病,全球约有1.5亿人受其影响。其特征是肝脏、骨骼肌和脂肪等外周组织存在胰岛素抵抗。胰岛素抵抗与肿瘤坏死因子α(TNF-α)水平升高有关,而TNF-α又会抑制胰岛素受体酪氨酸激酶的自身磷酸化。据报道,大麻可用于治疗糖尿病。一些报告表明,吸食大麻可降低糖尿病患者的血糖。Δ⁹-四氢大麻酚(THC)是大麻的主要精神活性成分。本研究旨在使用3T3-L1细胞确定亲脂性大麻提取物对脂肪生成的影响,并测量其对胰岛素抵抗脂肪细胞胰岛素敏感性的影响。在所有研究中,细胞均在含10%胎牛血清(FBS)的杜氏改良 Eagle 培养基(DMEM)中培养,并在3天内进行分化。在脂肪生成研究中,将分化后的细胞在有胰岛素和无胰岛素的情况下暴露于提取物中。随后测量脂质含量和葡萄糖摄取。随着THC浓度的增加,胰岛素诱导的葡萄糖摄取增加,而脂肪生成速率降低。使用TNF-α诱导胰岛素抵抗,将细胞暴露于提取物中并测量胰岛素诱导的葡萄糖摄取。暴露于提取物后,这些细胞中胰岛素诱导的葡萄糖摄取增加。提取核糖核酸(RNA)后进行半定量实时聚合酶链反应(RT-PCR),以评估提取物对葡萄糖转运蛋白4型(GLUT-4)、胰岛素受体底物-1(IRS-1)和IRS-2基因表达的影响。

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