Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes.
Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor Increases Circulating Zinc-Α2-Glycoprotein Levels in Patients with Type 2 Diabetes.
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2型糖尿病患者中循环的锌 - 葡萄糖共转运蛋白2（SGLT2）抑制剂增加了循环的锌-α2-糖蛋白水平。
DOI：
10.1038/srep32887
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发表时间：
2016-09-09
影响因子：
4.6
通讯作者：
Gao L
中科院分区：
文献类型：
--
作者：
Liao X;Wang X;Li H;Li L;Zhang G;Yang M;Yuan L;Liu H;Yang G;Gao L
ZAG 最近被认为是一种有效的代谢调节剂，但抗糖尿病药物对人类 ZAG 的影响仍不清楚。我们的目的是研究 SGLT2 抑制剂对 nT2DM 循环 ZAG 和 ADI 的影响。 162 名 nT2DM 受试者接受了安慰剂或 DAPA 治疗。 DAPA治疗3个月后，T2DM患者的HbA1c、FBG、2h-PBG、FFA、TG、血压、BMI、WHR、体重、FAT%、FINS和HOMA-IR显着下降，而HDL-C显着升高。重要的是，这些患者的循环 ZAG 和 ADI 水平在 DAPA 治疗后也显着增加。基础 ZAG 水平与治疗后 BMI、FAT%、TC、HbA1c、HDL-C 和 ADI 的变化相关，而基础 ADI 水平与 FAT%、TC、HbA1c、FFA 和 HDL-c 的变化相关。在体外，DAPA 处理显示 HepG2 细胞中 ZAG 表达和分泌增加。当与 PPAR-γ 抑制剂 GW9662 联合使用时，DAPA 对 ZAG 的作用被消除。这些发现表明循环ZAG可以受到DAPA的调节，并且DAPA通过激活PPAR-γ促进肝脏中ZAG的表达和分泌。 DAPA引起的ZAG变化可能在增强胰岛素敏感性方面发挥生理作用。
ZAG has recently been characterized as a potent metabolic regulator, but the effect of anti-diabetic agents on ZAG in humans remains unknown. Our aim was to study the effects of SGLT2 inhibitor on circulating ZAG and ADI in nT2DM. 162 subjects with nT2DM were treated by a placebo or DAPA. After 3-months of DAPA therapy, HbA1c, FBG, 2h-PBG, FFA, TG, blood pressure, BMI, WHR, body weight, FAT%, FINS, and HOMA-IR in T2DM patients decreased significantly, whereas HDL-C was significantly increased. Importantly, circulating ZAG and ADI levels in these patients were also significantly increased after DAPA therapy. Basal ZAG levels were associated with changes in BMI, FAT%, TC, HbA1c, HDL-C and ADI at post-treatment, whereas basal ADI levels were associated with changes in FAT%, TC, HbA1c, FFA and HDL-c. In vitro, DAPA treatment showed increased ZAG expression and secretion in HepG2 cells. When combined with a PPAR-γinhibitor GW9662, the effect of DAPA on ZAG was abrogated. These findings suggest that circulating ZAG can be regulated by DAPA, and DAPA promotes the expression and secretion of ZAG in the liver via the activation of PPAR-γ. The changes in ZAG induced by DAPA may play a physiologic role in enhancing insulin sensitivity.
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影响因子：
4.8
作者：
Russell, Steven T.;Tisdale, Michael J.
通讯作者：
Tisdale, Michael J.
影响因子：
8.2
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Albareda, M;Rodríguez-Espinosa, J;Corcoy, R
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Fonseca, Vivian A.;Ferrannini, Ele;Klasen, Sally
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作者：
Bradford, B. J.;Allen, M. S.
通讯作者：
Allen, M. S.