Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes.
Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes.
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DOI：
10.2337/dc13-0387
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发表时间：
2013-10
期刊：
影响因子：
16.2
通讯作者：
Griffen SC
中科院分区：
文献类型：
--
作者：
DeFronzo RA;Hompesch M;Kasichayanula S;Liu X;Hong Y;Pfister M;Morrow LA;Leslie BR;Boulton DW;Ching A;LaCreta FP;Griffen SC
采用胰腺/阶梯式高血糖钳夹（SHC）技术，检查达格列净（一种钠-葡萄糖协同转运蛋白2（SGLT 2）抑制剂）对肾脏葡萄糖重吸收主要成分（最大肾脏葡萄糖重吸收能力[TmG]降低、张开增加和阈值降低）的影响。2型糖尿病受试者（n = 12）和匹配的健康受试者（n = 12）在基线和达格列净治疗7天后接受胰腺/SHC（血糖范围5.5-30.5 mmol/L）。开发了一个药效学模型来描述两组肾脏葡萄糖重吸收的主要成分，然后用于根据个体葡萄糖滴定曲线估计这些参数。基线时，2型糖尿病受试者与对照组相比TmG、splay和阈值升高。达格列净治疗降低了两组的TmG和张开。然而，达格列净最显著的作用是降低2型糖尿病和对照受试者的葡萄糖排泄肾阈值。SGLT 2抑制剂达格列净通过降低TmG和葡萄糖经尿液排泄的阈值，改善糖尿病患者的血糖控制。
To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [TmG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. Subjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5–30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves. At baseline, type 2 diabetic subjects had elevated TmG, splay, and threshold compared with controls. Dapagliflozin treatment reduced the TmG and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects. The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the TmG and threshold at which glucose is excreted in the urine.
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影响因子：
168.9
作者：
Bailey, Clifford J.;Gross, Jorge L.;List, James F.
通讯作者：
List, James F.
影响因子：
6.7
作者：
Komoroski, B.;Vachharajani, N.;Pfister, M.
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Pfister, M.
影响因子：
7.7
作者：
Rahmoune, H;Thompson, PW;Brown, J
通讯作者：
Brown, J
影响因子：
6.1
作者：
Noonan, WT;Shapiro, VM;Banks, RO
通讯作者：
Banks, RO
影响因子：
16.2
作者：
List, James F.;Woo, Vincent;Fiedorek, Fred T.
通讯作者：
Fiedorek, Fred T.