Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.
Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.
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DOI：
10.2337/db10-0902
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发表时间：
2012-02
期刊：
影响因子：
7.7
通讯作者：
Spranger J
中科院分区：
文献类型：
--
作者：
Gögebakan Ö;Andres J;Biedasek K;Mai K;Kühnen P;Krude H;Isken F;Rudovich N;Osterhoff MA;Kintscher U;Nauck M;Pfeiffer AF;Spranger J
葡萄糖依赖性促胰岛素多肽（GIP）被认为对非胰岛组织有直接作用。据报道，在抑制细胞内可的松-皮质醇穿梭11β-羟基类固醇脱氢酶1型（11β-HSD 1）后，GIP还增加了脂肪细胞中的葡萄糖摄取和脂解抑制。本文分析了GIP是否改变脂质代谢，并进一步阐明了GIP、11β-HSD 1和脂肪酸代谢之间的关系。GIP以时间和剂量依赖性方式降低分化的3 T3-L1脂肪细胞中11 β-HSD 1启动子构建体的活性以及11β-HSD 1的表达和活性。这是通过减少游离脂肪酸（FFA）的释放和减少表达的关键酶调节脂肪组织中的脂解。预抑制11β-HSD 1可完全消除GIP诱导的FFA释放效应。为了研究GIP在人类中的急性作用，进行了随机临床试验。与生理盐水对照相比，GIP降低了循环FFA，并降低了皮下脂肪活检组织中11β-HSD 1的表达和离体活性以及脂肪甘油三酯脂肪酶的表达。我们的数据表明，GIP通过抑制脂解或增加再酯化作用减少脂肪组织FFA的释放。这一过程似乎依赖于11β-HSD 1活性的修饰。一般而言，所提供的数据支持GIP对脂肪组织具有直接和胰岛素非依赖性作用。
Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11β-HSD1, and fatty acid metabolism. GIP reduced activity of 11β-HSD1 promoter constructs and the expression and activity of 11β-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11β-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11β-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11β-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue.
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DOI：
10.1152/ajpendo.90769.2008
发表时间：
2009-02-01
影响因子：
5.1
作者：
Purnell, Jonathan Q.;Kahn, Steven E.;Brunzell, John D.
通讯作者：
Brunzell, John D.
影响因子：
7.7
作者：
Asmar M;Simonsen L;Madsbad S;Stallknecht B;Holst JJ;Bülow J
通讯作者：
Bülow J
影响因子：
7.7
作者：
Meier, JJ;Hüking, K;Nauck, MA
通讯作者：
Nauck, MA
影响因子：
8.2
作者：
Alberts, P;Engblom, L;Abrahmsén, L
通讯作者：
Abrahmsén, L
影响因子：
9.3
作者：
Yamaoka-Tojo, Minako;Tojo, Taiki;Izumi, Tohru
通讯作者：
Izumi, Tohru