Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul, 04401, Republic of Korea.
Hyonam Kidney Laboratory, Soonchunhyang University Seoul Hospital, 59 Daesagwan-ro, Yongsan-gu, Seoul, 04401, Republic of Korea.
Sci Rep. 2022 Nov 9;12(1):19103. doi: 10.1038/s41598-022-22083-6.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes in type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve the clinical outcomes remain elusive. We evaluated whether empagliflozin, an SGLT2 inhibitor, ameliorates mitochondrial dysfunction and inflammatory milieu of the kidneys in T2DM patients. We prospectively measured copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) and urinary interleukin-1β (IL-1β) in healthy volunteers (n = 22), in SGLT2 inhibitor-naïve T2DM patients (n = 21) at baseline, and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Both urinary mtDNA copy numbers and IL-1β levels were higher in the T2DM group than in healthy volunteers. Baseline copy numbers of serum mtCOX-3 in the T2DM group were lower than those in healthy volunteers. Empagliflozin induced marked reduction in both urinary and serum mtND-1 and mtCOX-3 copy numbers, as well as in urinary IL-1β. Empagliflozin could attenuate mitochondrial damage and inhibit inflammatory response in T2DM patients. This would explain the beneficial effects of SGLT2 inhibitors on cardiovascular and renal outcomes.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可改善 2 型糖尿病（T2DM）患者的心血管和肾脏结局。然而，SGLT2 抑制剂改善临床结局的机制仍不清楚。我们评估了 SGLT2 抑制剂恩格列净是否可改善 T2DM 患者的肾脏线粒体功能障碍和炎症环境。我们前瞻性地测量了健康志愿者（n=22）、SGLT2 抑制剂初治的 T2DM 患者（n=21，基线时）和接受恩格列净治疗 3 个月后的 T2DM 患者（n=17 接受 10mg 治疗或 n=4 接受 25mg 治疗）的尿和血清线粒体 DNA（mtDNA）烟酰胺腺嘌呤二核苷酸脱氢酶亚单位 1（mtND-1）和细胞色素-c 氧化酶 3（mtCOX-3）的拷贝数以及尿白细胞介素-1β（IL-1β）。T2DM 组的尿 mtDNA 拷贝数和 IL-1β 水平均高于健康志愿者。T2DM 组的血清 mtCOX-3 拷贝数在基线时低于健康志愿者。恩格列净可显著降低尿和血清 mtND-1 和 mtCOX-3 的拷贝数以及尿 IL-1β。恩格列净可减轻 T2DM 患者的线粒体损伤并抑制炎症反应。这可以解释 SGLT2 抑制剂对心血管和肾脏结局的有益作用。
