口服血清素通过被动肠道和绕道输送到全身循环改善2型糖尿病
Jun Zhang1, Fuping Wang1, Hailing Zhong1
1School of Pharmacy and Bioengineering, Chongqing University of Technology, 69 Hongguang Avenue, Chongqing, 400054, China.
Journal of ethnopharmacology
|May 16, 2024
概括
丝血清素 (SS) 抵抗消化,并通过被动和旁路运输被吸收到循环中,有效地治疗2型糖尿病 (T2DM). 这种天然蛋白质通过改善胰岛素耐药性和葡萄糖耐受性来显示T2DM的治疗益处.
科学领域:
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 来自丝虫子的丝素 (SS) 在传统中医中具有悠久的历史,用于治疗糖尿病.
- 最近的研究表明,SS对2型糖尿病 (T2DM) 具有治疗效益,可能通过影响胰腺小岛功能和胰岛素分泌.
- 胃肠道屏障对口服SS等蛋白质构成挑战,其吸收和全身循环不清楚.
研究的目的:
- 为了研究丝血清素 (SS) 穿越胃肠道屏障的机制.
- 为了确定SS是否在口服后进入全身循环.
- 通过循环评估SS在治疗2型糖尿病 (T2DM) 的治疗效果.
主要方法:
- 提取了丝素 (SS),并使用SDS-PAGE评估了其对模拟胃肠道消化的抵抗力.
- 实验室Caco-2细胞模型被用于分析SS传输机制,包括透性 (Papp) 和外细胞发生率 (ER),有或没有EDTA治疗.
- 2型糖尿病小鼠接受了口服或腹腔内施用SS,随后进行血度分析,葡萄糖和胰岛素水平测量以及胰腺组织检查.
主要成果:
- 在体外消化后,SS表现出良好的抗消化特性,分子量从10-25 kDa减少到10-15 kDa.
- SS 呈现出被动运输特征,具有高的 Papp (>1 × 10−6 cm·s−1) 和 ER (0.51.5),进一步增强了 EDTA,暗示绕道运输.
- 在T2DM小鼠中,口服SS给药导致胰岛素耐药性和葡萄糖耐受性得到改善,并部分吸收到循环中,尽管腹膜内注射显示出更高的疗效.
结论:
- 丝素 (SS) 在胃肠道中经历了部分酶分裂.
- 吸收的SS分子通过被动和膜运输机制进入循环.
- 这些被吸收的SS成分对2型糖尿病 (T2DM) 产生治疗作用.
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