Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte via promoting AMPK phosphorylation.
Metformin inhibits expression and secretion of PEDF in adipocyte and hepatocyte via promoting AMPK phosphorylation.
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二甲双胍通过促进 AMPK 磷酸化抑制脂肪细胞和肝细胞中 PEDF 的表达和分泌。
DOI：
10.1155/2013/429207
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发表时间：
2013
影响因子：
4.6
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Yang S;Lv Q;Luo T;Liu L;Gao R;Chen S;Ye P;Cheng Q;Li Q
目标。色素上皮衍生因子(PEDF)在肥胖诱导的胰岛素抵抗(IR)中起重要作用。本研究旨在研究广泛使用的改善胰岛素抵抗的药物二甲双胍在体内和体外对PEDF产生的影响。方法：研究方法。将SD大鼠分为正常对照组、高脂组(HF组)和二甲双胍组(MET组)。采用高胰岛素正血糖钳夹技术评价胰岛素敏感性。建立3T3-L1和HepG2细胞IR模型，分别用二甲双胍和AMPK抑制剂进行治疗。结果。在体内，HF组血清PEDF升高，与胰岛素敏感性呈负相关，而MET组血清PEDF降低，脂肪和肝脏PEDF表达下调，IR显著改善。在体外，IR细胞的PEDF分泌和表达增加，而二甲双胍则降低PEDF的分泌和表达，并伴有葡萄糖摄取增加。二甲双胍可促进肥胖大鼠脂肪和肝脏中AMPK的磷酸化，而在体外，当与AMPK抑制剂联合使用时，二甲双胍对PEDF的作用被取消。结论。二甲双胍通过促进AMPK的磷酸化，抑制脂肪和肝脏中PEDF的表达和分泌，这与IR的改善密切相关。
Objective. Pigment epithelium-derived factor (PEDF) plays an important role in obesity-induced insulin resistance (IR). The study aims to investigate the effect of metformin, a widely used agent to improve IR, on PEDF production both in vivo and in vitro. Methods. SD rats were divided into normal control group, high fat group (HF group), and metformin group (MET group). Hyperinsulinemic euglycemic clamp was performed to evaluate insulin sensitivity. IR models of 3T3-L1 and HepG2 cells were established and then treated with metformin and inhibitor of AMP activated protein kinase (AMPK). Results. In vivo, the HF group showed increased serum PEDF which is negatively correlated with insulin sensitivity, while the MET group revealed decreased serum PEDF and downregulated PEDF expression in fat and liver, concomitant with significantly improved IR. In vitro, the IR cells showed enhanced PEDF secretion and expression, whereas metformin lowered PEDF secretion and expression, accompanied with increased glucose uptake. Metformin stimulated AMPK phosphorylation in fat and liver of the obese rats, while in vitro, when combined with AMPK inhibitor, the effect of metformin on PEDF was abrogated. Conclusions. Metformin inhibits the expression and secretion of PEDF in fat and liver via promoting AMPK phosphorylation, which is closely associated with IR improvement.
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影响因子：
29
作者：
Crowe, Seamus;Wu, Lindsay E.;Watt, Matthew J.
通讯作者：
Watt, Matthew J.
影响因子：
4.8
作者：
Liu, Hui-Yu;Cao, Sophia Y.;Cao, Wenhong
通讯作者：
Cao, Wenhong
DOI：
10.1152/ajpheart.01269.2005
发表时间：
2006-07-01
影响因子：
4.8
作者：
Bertrand, L;Ginion, A;Vanoverschelde, JL
通讯作者：
Vanoverschelde, JL
影响因子：
4.9
作者：
Famulla, S.;Lamers, D.;Eckel, J.
通讯作者：
Eckel, J.
影响因子：
3.1
作者：
Wang, Lan;Xu, Ming Lu;Wang, Myeong-Hyeon
通讯作者：
Wang, Myeong-Hyeon