Department of Clinical and Translational Sciences, Marshall University, Huntington, WV, USA.
J Nutr. 2020 Apr 1;150(4):747-755. doi: 10.1093/jn/nxz277.
Chronic alcohol use often leads to malnutrition. However, how the intestinal absorption of nutrients such as glucose may be affected during moderate ethanol use has not been investigated. Glucose is absorbed via sodium (Na)-dependent glucose co-transport (SGLT1; SLC5A1) along the brush border membrane (BBM) of intestinal absorptive villus cells.
The aim of this study was to investigate how moderate alcohol consumption affects the absorption of glucose via SGLT1.
Intestinal epithelial cells (IEC-18; rat) were exposed to 8.64 mM ethanol over 1, 3, 6, and 12 h. Rats (16-wk-old, male, Sprague-Dawley) were administered 2 g/kg ethanol over 1, 3, and 6 h. Na-dependent 3H-O-methyl-d-glucose uptake was measured to assess SGLT1 activity. Na-K-ATPase activity was measured as a function of inorganic phosphate release. Protein expression was analyzed by Western blot analysis and immunohistochemical staining.
Ethanol significantly decreased Na-dependent glucose absorption in enterocytes in vitro (ethanol treatment: 48.4% of controls at 1 h; P < 0.01) and in vivo (ethanol treatment: 60.0% of controls at 1 h; P < 0.01). Na-K-ATPase activity was significantly inhibited in vitro (ethanol treatment: 36.9% of controls at 1 h; P < 0.01) and in vivo (ethanol treatment: 42.1% of controls at 1 h; P < 0.01). Kinetic studies showed that the mechanism of inhibition of Na-glucose co-transport was secondary to a decrease in the affinity (1/Km) of the co-transporter for glucose both in vitro and in vivo. Western blots and immunohistochemistry further demonstrated unaltered amounts of SGLT1 after ethanol treatment.
Moderate ethanol significantly decreases glucose absorption in IEC-18 cells and in villus cells of Sprague-Dawley rats. The inhibition of SGLT1 is secondary to an altered Na gradient at the cellular level and secondary to diminished affinity of the co-transporter for glucose at the protein level in the BBM. These observations may, at least in part, explain 1 possible mechanism of the onset of malnutrition associated with alcohol consumption.
慢性酒精使用通常会导致营养不良。然而，中等剂量乙醇使用时，肠道对葡萄糖等营养物质的吸收如何受到影响，尚未得到研究。葡萄糖通过肠吸收绒毛细胞的刷状缘膜（BBM）上的钠（Na）依赖性葡萄糖协同转运（SGLT1；SLC5A1）进行吸收。
本研究旨在探讨中度酒精摄入如何影响 SGLT1 对葡萄糖的吸收。
将肠上皮细胞（IEC-18；大鼠）暴露于 8.64 mM 乙醇中 1、3、6 和 12 小时。给予 16 周龄雄性 Sprague-Dawley 大鼠 2 g/kg 乙醇 1、3 和 6 小时。通过测量 3H-O-甲基-d-葡萄糖摄取来评估 SGLT1 活性。测量无机磷酸盐释放作为 Na-K-ATPase 活性的函数。通过 Western blot 分析和免疫组织化学染色分析蛋白质表达。
乙醇在体外显著降低肠细胞中 Na 依赖性葡萄糖吸收（乙醇处理：1 小时时为对照的 48.4%；P < 0.01）和体内（乙醇处理：1 小时时为对照的 60.0%；P < 0.01）。体外（乙醇处理：1 小时时为对照的 36.9%；P < 0.01）和体内（乙醇处理：1 小时时为对照的 42.1%；P < 0.01），Na-K-ATPase 活性均受到显著抑制。动力学研究表明，Na-葡萄糖协同转运的抑制机制是由于协同转运体对葡萄糖的亲和力（1/Km）降低所致，无论是在体外还是体内。Western blot 和免疫组织化学进一步表明，乙醇处理后 SGLT1 的含量没有变化。
中等剂量的乙醇可显著降低 IEC-18 细胞和 Sprague-Dawley 大鼠绒毛细胞的葡萄糖吸收。SGLT1 的抑制是由于细胞水平 Na 梯度的改变以及 BBM 中协同转运体对葡萄糖亲和力的降低所致。这些观察结果至少可以部分解释与酒精摄入相关的营养不良发生的 1 种可能机制。
