Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity.
Mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity.
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DOI：
10.2337/db08-1428
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发表时间：
2009-04
期刊：
影响因子：
7.7
通讯作者：
Gardiner JV
中科院分区：
文献类型：
--
作者：
Bewick GA;Kent A;Campbell D;Patterson M;Ghatei MA;Bloom SR;Gardiner JV
Ghrelin是唯一已知的增加摄食行为的外周激素。然而，其在能量稳态的生理调节中的作用尚不清楚，因为生长素释放肽或其受体的缺失不会改变正常饮食喂养的小鼠的食物摄入或体重。我们假设生长素释放肽在其生理组织中的过度表达会增加食物摄入和体重。我们使用细菌人工染色体转基因来产生胃和脑中生长素释放肽表达和产生增加的小鼠模型。我们研究了生长素释放肽过表达对食物摄入和体重的影响。我们还测量了能量消耗，并确定了葡萄糖耐量，葡萄糖刺激的胰岛素释放和外周胰岛素敏感性。生长素释放肽转基因（Tg）小鼠表现出循环生物活性生长素释放肽增加，其与摄食过多、能量消耗增加、葡萄糖耐受不良、葡萄糖刺激的胰岛素分泌减少和瘦素敏感性降低相关。这是Tg方法的第一份报告，表明ghrelin在正常进食条件下调节食欲，并提供了ghrelin在调节β细胞功能中起重要作用的证据。
Ghrelin is the only known peripheral hormone to increase ingestive behavior. However, its role in the physiological regulation of energy homeostasis is unclear because deletion of ghrelin or its receptor does not alter food intake or body weight in mice fed a normal chow diet. We hypothesized that overexpression of ghrelin in its physiological tissues would increase food intake and body weight. We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in the stomach and brain. We investigated the effect of ghrelin overexpression on food intake and body weight. We also measured energy expenditure and determined glucose tolerance, glucose stimulated insulin release, and peripheral insulin sensitivity. Ghrelin transgenic (Tg) mice exhibited increased circulating bioactive ghrelin, which was associated with hyperphagia, increased energy expenditure, glucose intolerance, decreased glucose stimulated insulin secretion, and reduced leptin sensitivity. This is the first report of a Tg approach suggesting that ghrelin regulates appetite under normal feeding conditions and provides evidence that ghrelin plays a fundamental role in regulating β-cell function.
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影响因子：
4.9
作者：
Liu, Y-L;Semjonous, N. M.;Bloom, S. R.
通讯作者：
Bloom, S. R.
影响因子：
7.7
作者：
Dezaki, K;Hosoda, H;Yada, T
通讯作者：
Yada, T
影响因子：
4.8
作者：
Ariyasu, H;Takaya, K;Nakao, K
通讯作者：
Nakao, K
DOI：
10.1073/pnas.0305930101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Sun, YX;Wang, P;Smith, RG
通讯作者：
Smith, RG
影响因子：
4.8
作者：
Thomas, GB;Fairhall, KM;Robinson, ICAF
通讯作者：
Robinson, ICAF