Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
Direct angiotensin II type 2 receptor stimulation ameliorates insulin resistance in type 2 diabetes mice with PPARγ activation.
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直接血管紧张素II类型2受体刺激可以通过PPARγ激活来缓解2型糖尿病小鼠的胰岛素抵抗。
DOI：
10.1371/journal.pone.0048387
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Horiuchi M
中科院分区：
文献类型：
--
作者：
Ohshima K;Mogi M;Jing F;Iwanami J;Tsukuda K;Min LJ;Ogimoto A;Dahlöf B;Steckelings UM;Unger T;Higaki J;Horiuchi M
血管紧张素II 2型（AT 2）受体的刺激在胰岛素抵抗的发病机制中的作用仍不清楚。因此，我们检查了化合物21（C21）的直接AT 2受体刺激可能有助于具有PPARγ活化的2型糖尿病（T2 DM）中可能的胰岛素增敏/抗糖尿病作用的可能性，主要集中在脂肪组织。T2 DM小鼠KK-Ay腹腔注射C21和/或PPARγ拮抗剂GW 9662饮水2周。通过口服葡萄糖耐量试验、胰岛素耐量试验和白色脂肪组织中2-[3 H]脱氧-D-葡萄糖的摄取来评估胰岛素抵抗。观察脂肪组织形态学变化、脂肪细胞分化及炎症反应。C21治疗可改善KK-Ay小鼠的胰岛素抵抗，而不影响血压，至少部分是通过对PPARγ通路的影响。C21处理增加血清脂联素浓度并降低TNF-α浓度;然而，通过与GW 9662联合处理，这些作用被PPARγ阻断剂减弱。此外，我们观察到给予C21可增强脂肪细胞分化和PPARγ DNA结合活性，并降低白色脂肪组织中的炎症，而C21的这些作用可通过与GW 9662共同处理而减弱。我们还观察到给予C21恢复了糖尿病胰腺组织中的β细胞损伤。目前的研究表明，C21直接刺激AT 2受体并伴有PPARγ活化可改善T2 DM小鼠的胰岛素抵抗，至少部分是由于改善脂肪细胞功能障碍和保护胰腺β细胞。
The role of angiotensin II type 2 (AT2) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT2 receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue. T2DM mice, KK-Ay, were subjected to intraperitoneal injection of C21 and/or a PPARγ antagonist, GW9662 in drinking water for 2 weeks. Insulin resistance was evaluated by oral glucose tolerance test, insulin tolerance test, and uptake of 2-[3H] deoxy-D-glucose in white adipose tissue. Morphological changes of adipose tissues as well as adipocyte differentiation and inflammatory response were examined. Treatment with C21 ameliorated insulin resistance in KK-Ay mice without influencing blood pressure, at least partially through effects on the PPARγ pathway. C21 treatment increased serum adiponectin concentration and decreased TNF-α concentration; however, these effects were attenuated by PPARγ blockade by co-treatment with GW9662. Moreover, we observed that administration of C21 enhanced adipocyte differentiation and PPARγ DNA-binding activity, with a decrease in inflammation in white adipose tissue, whereas these effects of C21 were attenuated by co-treatment with GW9662. We also observed that administration of C21 restored β cell damage in diabetic pancreatic tissue. The present study demonstrated that direct AT2 receptor stimulation by C21 accompanied with PPARγ activation ameliorated insulin resistance in T2DM mice, at least partially due to improvement of adipocyte dysfunction and protection of pancreatic β cells.
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炎症和代谢疾病中的脂肪因子。
DOI：
10.1038/nri2921
发表时间：
2011-02
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1111/j.1463-1326.2010.01299.x
发表时间：
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期刊：
Diabetes, obesity & metabolism
影响因子：
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作者：
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通讯作者：
Evans-Molina C
影响因子：
4.9
作者：
Kjeldsen, Sverre E.;Julius, Stevo;Zanchetti, Alberto
通讯作者：
Zanchetti, Alberto
影响因子：
168.9
作者：
Dormandy, JA;Charbonnel, B;Taton, J
通讯作者：
Taton, J
影响因子：
12.4
作者：
Cawthorn, W. P.;Heyd, F.;Hegyi, K.;Sethi, J. K.
通讯作者：
Sethi, J. K.