Mitsuoka Keisuke, Hayashizaki Yuka, Murakami Yoshihiro, Takasu Toshiyuki, Yokono Masanori, Umeda Nobuhiro, Takakura Shoji, Noda Akihiro, Miyoshi Sosuke
Drug Discovery Research Astellas Pharma Inc. Tsukuba Japan.
Pharmacol Res Perspect. 2016 Jul 1;4(4):e00244. doi: 10.1002/prp2.244. eCollection 2016 Aug.
Sodium-dependent glucose cotransporter 2 (SGLT2) is a pharmacological target of type 2 diabetes mellitus. The aim of this study was to noninvasively visualize the pharmacological action of a selective SGLT2 inhibitor ipragliflozin in the kidney using positron emission tomography (PET) imaging with C-methyl-d-glucoside (C-MDG), an SGLT-specific radio-labeled substrate. PET imaging with C-MDG in vehicle-treated rats demonstrated that intravenously injected C-MDG substantially accumulated in the renal cortex, reflecting that the compound was reabsorbed by SGLTs. In contrast, ipragliflozin-treated rats showed significantly lower uptake of C-MDG in renal cortex in a dose-related manner, suggesting that ipragliflozin inhibited the renal reabsorption of C-MDG. This method of visualizing the mode of action of an SGLT2 inhibitor in vivo has demonstrated the drug's mechanism in reducing renal glucose reabsorption in kidney in living animals.
钠依赖性葡萄糖协同转运蛋白2（SGLT2）是2型糖尿病的一个药理学靶点。本研究的目的是使用正电子发射断层扫描（PET）成像技术，以SGLT特异性放射性标记底物C-甲基-D-葡萄糖苷（C-MDG），在肾脏中无创可视化选择性SGLT2抑制剂依帕列净的药理作用。在给予赋形剂处理的大鼠中进行的C-MDG PET成像显示，静脉注射的C-MDG在肾皮质大量蓄积，这反映该化合物被SGLTs重吸收。相比之下，依帕列净处理的大鼠肾皮质中C-MDG的摄取以剂量相关方式显著降低，表明依帕列净抑制了C-MDG的肾脏重吸收。这种在体内可视化SGLT2抑制剂作用模式的方法，已证明该药物在活体动物中减少肾脏葡萄糖重吸收的机制。
