Functional imaging of pharmacological action of SGLT2 inhibitor ipragliflozin via PET imaging using ¹¹C-MDG.

ABSTRACT: 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 ¹¹C-methyl-d-glucoside (¹¹C-MDG), an SGLT-specific radio-labeled substrate. PET imaging with ¹¹C-MDG in vehicle-treated rats demonstrated that intravenously injected ¹¹C-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 ¹¹C-MDG in renal cortex in a dose-related manner, suggesting that ipragliflozin inhibited the renal reabsorption of ¹¹C-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.

SUBMITTER: Mitsuoka K 

PROVIDER: S-EPMC5242169 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature