Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University.
Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University.
Biol Pharm Bull. 2024;47(9):1477-1483. doi: 10.1248/bpb.b24-00247.
Salmon milt extract (SME) is rich in nucleotides, especially deoxyribonucleoside monophosphates (dNMPs), which has the potential to exert anti-obesity effects. Sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) are responsible for absorbing sugar from the small intestine. The purpose of this study was to examine the effects of SME on the functions of SGLT1 and GLUT2 and elucidate the mechanisms underlying the inhibition of glucose absorption by SME. We investigated the effect of SME on the expression and function of intestinal glucose transporters, using differentiated Caco-2 cells. SME treatment decreased the expression SGLT1 and GLUT2 mRNA and protein in Caco-2 cells. [C]-Labelled methyl-α-D-glucopyranoside and [H]-labelled 2-deoxy-D-glucose (DG) uptake into Caco-2 cells was significantly reduced by SME treatment. Similarly, the dNMP mixture containing the four mononucleotides 2'-deoxyadenosine 5'-monophosphate (dAMP), 2'-deoxyguanosine 5'-monophosphate (dGMP), 2'-deoxycytidine 5'-monophosphate (dCMP), and 2'-deoxythymidine 5'-monophosphate (dTMP) decreased SGLT1 and GLUT2 expression. dNMP mixture-induced reduction in the mRNA expression of these transporters was suppressed when exposed to the mixture without dTMP. Furthermore, dNMP mixture-induced alterations in the expression of hepatocyte nuclear factor (HNF)-1α and HNF1β, which have been characterized as modulators of both transporters also showed a similar trend. dTMP treatment alone decreased GLUT2 expression, resulting in reduced [H] DG uptake by Caco-2 cells. SME decreased the expression of HNF1α, HNF1β, and its targets SGLT1 and GLUT2, resulting in reduced glucose uptake by Caco-2 cells. In addition, our results revealed that dTMP plays an important role in suppressing the expression of intestinal glucose transporters.
精子鱼精提取物（SME）富含核苷酸，特别是脱氧核苷单磷酸（dNMP），具有发挥抗肥胖作用的潜力。钠依赖性葡萄糖转运蛋白 1（SGLT1）和葡萄糖转运蛋白 2（GLUT2）负责从小肠吸收糖。本研究旨在研究 SME 对 SGLT1 和 GLUT2 功能的影响，并阐明 SME 抑制葡萄糖吸收的机制。我们使用分化的 Caco-2 细胞研究 SME 对肠道葡萄糖转运蛋白表达和功能的影响。SME 处理降低了 Caco-2 细胞中 SGLT1 和 GLUT2 mRNA 和蛋白的表达。SME 处理显著减少了 Caco-2 细胞中 [C]-标记的甲基-α-D-吡喃葡萄糖苷和 [H]-标记的 2-脱氧-D-葡萄糖（DG）的摄取。同样，含有四种单核苷酸 2'-脱氧腺苷 5'-单磷酸（dAMP）、2'-脱氧鸟苷 5'-单磷酸（dGMP）、2'-脱氧胞苷 5'-单磷酸（dCMP）和 2'-脱氧胸苷 5'-单磷酸（dTMP）的 dNMP 混合物降低了 SGLT1 和 GLUT2 的表达。当暴露于不含 dTMP 的混合物时，dNMP 混合物诱导的这些转运体的 mRNA 表达减少被抑制。此外，dNMP 混合物诱导的肝核因子（HNF）-1α和 HNF1β表达的改变，这两种因子均被表征为两种转运体的调节剂，也表现出相似的趋势。dTMP 单独处理降低了 GLUT2 的表达，导致 Caco-2 细胞中 [H]DG 的摄取减少。SME 降低了 HNF1α、HNF1β 及其靶标 SGLT1 和 GLUT2 的表达，导致 Caco-2 细胞中葡萄糖摄取减少。此外，我们的结果表明 dTMP 在抑制肠道葡萄糖转运蛋白的表达中起重要作用。
