Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25701, USA.
Nutrients. 2020 Oct 13;12(10):3116. doi: 10.3390/nu12103116.
In mammalian small intestine, glucose is primarily absorbed via Na-dependent glucose co-transporter (SGLT1) on the brush border membrane (BBM) of absorptive villus cells. Malabsorption of nutrients (e.g., glucose) leads to malnutrition, a common symptom of inflammatory bowel disease (IBD), where the mucosa is characterized by chronic inflammation. Inducible nitric oxide (iNO) is known to be elevated in IBD mucosa. SAMP1/YitFc (SAMP1) mouse is a spontaneous model of chronic ileitis that develops lesions in its terminal ileum, very similar to human IBD. How SGLT1 may be affected in SAMP1 model of chronic ileitis is unknown. Ten-week-old SAMP1 mice with AKR mice as control were treated with N6-(1-iminoethyl)-L-lysine dihydrochloride (L-NIL) to inhibit iNO production. Intracellular NO levels were found to be increased in villus cells from SAMP1 mice. Moreover, SGLT1 and NaK-ATPase activities and BBM SGLT1 expression were significantly decreased. However, L-NIL treatment reduced the intracellular iNO production, and reversed both downregulated SGLT1 and Na/K-ATPase activities in SAMP1 mice. Inhibition of iNO by L-NIL treatment also significantly reversed the BBM SGLT1 protein expression in SAMP1 mice. L-NIL reversed the inflammation mediated downregulation of SGLT1 activity by restoring the BBM SGLT1 expression. Thus, regulation of SGLT1 in chronic ileitis is likely mediated by iNO.
在哺乳动物的小肠中，葡萄糖主要通过吸收性绒毛细胞的刷状缘膜（BBM）上的钠依赖性葡萄糖协同转运蛋白（SGLT1）进行吸收。营养物质（例如葡萄糖）吸收不良会导致营养不良，这是炎症性肠病（IBD）的常见症状，其中黏膜的特征是慢性炎症。已知诱导型一氧化氮（iNO）在 IBD 黏膜中升高。SAMP1/YitFc（SAMP1）小鼠是一种自发性慢性回肠炎模型，其末端回肠会出现病变，非常类似于人类的 IBD。SGLT1 在 SAMP1 慢性回肠炎模型中如何受到影响尚不清楚。将 10 周龄的 SAMP1 小鼠与 AKR 小鼠作为对照，用 N6-（1-亚氨基乙基）-L-赖氨酸二盐酸盐（L-NIL）治疗以抑制 iNO 产生。发现 SAMP1 小鼠的绒毛细胞内 NO 水平升高。此外，SGLT1 和 NaK-ATPase 活性以及 BBM SGLT1 表达显著降低。然而，L-NIL 治疗降低了 SAMP1 小鼠的细胞内 iNO 产生，并逆转了 SGLT1 和 Na/K-ATPase 活性的下调。L-NIL 抑制 iNO 的治疗也显著逆转了 SAMP1 小鼠的 BBM SGLT1 蛋白表达。通过恢复 BBM SGLT1 表达，L-NIL 逆转了由炎症介导的 SGLT1 活性下调。因此，慢性回肠炎中 SGLT1 的调节可能是由 iNO 介导的。
