Exenatide improves glucocorticoid-induced glucose intolerance in mice.
Exenatide improves glucocorticoid-induced glucose intolerance in mice.
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DOI：
10.2147/dmso.s15510
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发表时间：
2011-01-26
期刊：
影响因子：
--
通讯作者：
Yeung SC
中科院分区：
文献类型：
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作者：
Zhao R;Fuentes-Mattei E;Velazquez-Torres G;Su CH;Chen J;Lee MH;Yeung SC
艾塞那肽是一种模拟肠促胰岛素的药物，最近在美国用于治疗糖尿病。关于艾塞那肽在糖皮质激素（GC）诱导的糖尿病中的作用的信息缺乏。虽然之前已经研究了连续静脉输注艾塞那肽对口服强的松龙的健康男性gc诱导的葡萄糖耐受不良的影响，但我们研究了单次皮下剂量（3 μg/kg）艾塞那肽对gc诱导的C57BL/6小鼠葡萄糖耐受不良的降血糖效果。在纵向实验中，口服葡萄糖耐量试验（OGTT）的曲线下面积（AUC）在地塞米松治疗后显著升高（P = 0.004），艾塞那肽治疗后降低（P < 0.001）。横断面实验表明，在地塞米松诱导的葡萄糖耐受不良小鼠模型中，与安慰剂相比，艾塞那肽改善了葡萄糖耐受。艾塞那肽组OGTT AUC显著低于安慰剂组（P < 0.001）。胰岛素耐量试验（ITT）表明，与安慰剂相比，艾塞那肽降低了小鼠对胰岛素的耐受性。艾塞那肽组ITT的AUC也显著低于安慰剂组（P = 0.006）。总之，在这些安慰剂对照实验中，单剂量的艾塞那肽能够降低葡萄糖耐受不良和胰岛素抵抗。未来的临床试验有理由研究艾塞那肽在治疗gc诱导的葡萄糖不耐受/糖尿病中的作用。
Exenatide is an incretin mimetic that is recently available in the US for the treatment of diabetes. There is a paucity of information on the effects of exenatide in glucocorticoid (GC)-induced diabetes. Although the effect of continuous intravenous infusion of exenatide on GC-induced glucose intolerance has been investigated before in healthy human males receiving oral prednisolone, we investigated the efficacy of a single subcutaneous dose of exenatide (3 μg/kg) in lowering blood glucose in GC-induced glucose intolerance in C57BL/6 mice. In a longitudinal experiment, the area under the curve (AUC) of oral glucose tolerance tests (OGTT) significantly increased after dexamethasone (P = 0.004), which was subsequently decreased by exenatide (P < 0.001). A cross-sectional experiment showed that exenatide improved glucose tolerance compared with placebo in a mouse model of dexamethasone-induced glucose intolerance. AUC of OGTT in the exenatide group were significantly (P < 0.001) lower than in the placebo group. Insulin tolerance tests (ITT) demonstrated that exenatide decreased the ability of the mice to tolerate insulin compared with placebo. The AUC of ITT in the exenatide group were also significantly (P = 0.006) lower than in the placebo group. In conclusion, a single dose of exenatide was able to decrease glucose intolerance and insulin resistance in these placebo-controlled experiments. Future clinical trials are justified to investigate the role of exenatide in the treatment of GC-induced glucose intolerance/diabetes.