Effect of ghrelin on glucose regulation in mice
Effect of ghrelin on glucose regulation in mice
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DOI：
10.1152/ajpendo.00445.2011
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发表时间：
2012-05-01
影响因子：
5.1
通讯作者：
Sunehag, Agneta L.
中科院分区：
文献类型：
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作者：
Chacko, Shaji K.;Haymond, Morey W.;Sunehag, Agneta L.
Chacko SK，Haymond MW，Sun Y，Marini JC，Sauer PJJ，Ma X，Sunehag AL. Ghrelin对小鼠血糖调节的影响. Am J Physiol Endocrinol Metab 302：E1055-E1062，2012.首次发表于2011年2月14日; doi：10.1152/ajpendo.00445.2011。减肥手术后葡萄糖代谢的改善似乎是多种循环肠道激素浓度改变的复合效应。然而，它们在不同条件下对葡萄糖代谢的个体影响尚不清楚。本研究的目的是确定ghrelin是否对糖原分解、糖原生成和胰岛素敏感性有影响（使用小鼠模型）。在吸收后状态的野生型（WT）、ghrelin敲除（ghrelin（-/-））和生长激素促分泌素受体敲除（Ghsr（-/-））小鼠中测量葡萄糖出现率、糖原分解和糖原生成。禁食条件的生理性质通过在黑暗周期结束时立即开始的短期禁食来确定。测定血糖和胰岛素浓度，计算胰岛素抵抗和肝脏胰岛素敏感性。在食物剥夺期间，各组之间的葡萄糖浓度没有差异。然而，ghrelin（-/-）和Ghsr（-/-）小鼠的血浆胰岛素浓度低于WT小鼠。在吸收后状态下，Ghrelin（-/-）和Ghsr（-/-）小鼠的胰岛素生成率、糖原分解率和胰岛素敏感性指数均高于WT小鼠。Ghrelin（-/-）和Ghsr（-/-）小鼠肝组织胰岛素受体底物1和葡萄糖转运蛋白2基因表达均高于WT小鼠。这项研究表明，在小鼠中，通过消除生长激素释放肽或生长激素促分泌素受体，可以增加糖原合成和糖原分解，改善胰岛素敏感性。
Chacko SK, Haymond MW, Sun Y, Marini JC, Sauer PJJ, Ma X, Sunehag AL. Effect of ghrelin on glucose regulation in mice. Am J Physiol Endocrinol Metab 302: E1055-E1062, 2012. First published February 14, 2011; doi:10.1152/ajpendo.00445.2011.-Improvement of glucose metabolism after bariatric surgery appears to be from the composite effect of the alterations in multiple circulating gut hormone concentrations. However, their individual effect on glucose metabolism during different conditions is not clear. The objective of this study was to determine whether ghrelin has an impact on glycogenolysis, gluconeogenesis, and insulin sensitivity (using a mice model). Rate of appearance of glucose, glycogenolysis, and gluconeogenesis were measured in wild-type (WT), ghrelin knockout (ghrelin(-/-)), and growth hormone secretagogue receptor knockout (Ghsr(-/-)) mice in the postabsorptive state. The physiological nature of the fasting condition was ascertained by a short-term fast commenced immediately at the end of the dark cycle. Concentrations of glucose and insulin were measured, and insulin resistance and hepatic insulin sensitivity were calculated. Glucose concentrations were not different among the groups during the food-deprived period. However, plasma insulin concentrations were lower in the ghrelin(-/-) and Ghsr(-/-) than WT mice. The rates of gluconeogenesis, glycogenolysis, and indexes of insulin sensitivity were higher in the ghrelin(-/-) and Ghsr(-/-) than WT mice during the postabsorptive state. Insulin receptor substrate 1 and glucose transporter 2 gene expressions in hepatic tissues of the ghrelin(-/-) and Ghsr(-/-) were higher compared with that in WT mice. This study demonstrates that gluconeogenesis and glycogenolysis are increased and insulin sensitivity is improved by the ablation of the ghrelin or growth hormone secretagogue receptor in mice.