Acute and chronic SGLT-2 inhibition increase endogenous glucose production (EGP). However, the organ - liver versus kidney - responsible for the increase in EGP has not been identified. 20 T2DM and 12 NGT subjects received [3-3H]-glucose infusion (to measure total EGP) in combination with arterial and renal vein catheterization and PAH infusion for determination of renal blood flow. Total EGP, net renal arteriovenous balance, and renal glucose production were measured before and 4 hours after dapagliflozin and placebo administration. Following DAPA, EGP increased in both T2D and NGT from baseline to 240 minutes, while there was a significant time-related decrease after placebo in T2D. Renal glucose production at baseline was <5% of basal EGP in both groups and did not change significantly following DAPA in either NGT and T2D. Renal glucose uptake (sum of tissue glucose uptake plus glucosuria) increased in both T2D and NGT following DAPA (P<0.05 vs placebo). The increase in RGU was entirely explained by the increase in glucosuria. Single dose of dapagliflozin significantly increased EGP, which primarily is explained by an increase in hepatic glucose production, establishing the existence of a novel renal-hepatic axis.

中文翻译：

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达格列净对 T2DM 和 NGT 受试者肾和肝血糖动力学的影响

急性和慢性 SGLT-2 抑制会增加内源性葡萄糖产生 (EGP)。然而，导致 EGP 增加的器官（肝脏与肾脏）尚未确定。 20 名 T2DM 和 12 名 NGT 受试者接受 [3-3H]-葡萄糖输注（以测量总 EGP），并结合动脉和肾静脉导管插入术以及 PAH 输注以确定肾血流量。在达格列净和安慰剂给药之前和之后4小时测量总EGP、净肾动静脉平衡和肾葡萄糖产生。 DAPA 治疗后，T2D 和 NGT 的 EGP 从基线增加到 240 分钟，而 T2D 服用安慰剂后，EGP 出现显着的时间相关下降。两组中基线时的肾葡萄糖产生均＜基础EGP的5％，并且在NGT和T2D中DAPA后没有显着变化。 DAPA 后 T2D 和 NGT 中肾葡萄糖摄取（组织葡萄糖摄取加上糖尿的总和）均增加（与安慰剂相比，P＜0.05）。 RGU 的增加完全由糖尿的增加来解释。单剂量达格列净显着增加 EGP，这主要是通过肝脏葡萄糖产生的增加来解释的，从而确立了新的肾-肝轴的存在。