Glucose metabolism in vivo in four commonly used inbred mouse strains.

Glucose metabolism in vivo in four commonly used inbred mouse strains.
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在四种常用的近交小鼠菌株中的体内葡萄糖代谢。

DOI:
10.2337/db07-1615
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发表时间:
2008-07
期刊:
影响因子:
7.7
通讯作者:
Wasserman, David H.
Wasserman, David H.
中科院分区:
医学1区
文献类型:
--
作者:
Berglund, Eric D.;Li, Candice Y.;Poffenberger, Greg;Ayala, Julio E.;Fueger, Patrick T.;Willis, Shannon E.;Jewell, Marybeth M.;Powers, Alvin C.;Wasserman, David H.

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目的-表征常用近交系小鼠品系之间全身葡萄糖代谢的差异。研究设计和方法-高胰岛素血症-正常血糖(≥ 8.5 mmol/l)和低血糖(≥ 3.0 mmol/l)钳夹在插管,5小时禁食小鼠中进行,以评估胰岛素作用和低血糖反调节反应。进行高血糖钳夹(> 15 mmol/l)以评估胰岛素分泌,并与灌注胰岛的结果进行比较。胰岛素作用和低血糖反调节和胰岛素分泌表型在四个近交系小鼠品系中差异很大。体内胰岛素分泌在129 X1/Sv小鼠中最大,但对低血糖的反调节反应减弱。体内FVB/N小鼠未显示葡萄糖刺激的胰岛素分泌增加、相对肝脏胰岛素抵抗和对低血糖的最高反调节反应。在DBA/2小鼠中,胰岛素作用在各品系中最低,并且分离的胰岛在体外具有最大的葡萄糖刺激的胰岛素分泌。在C57 BL/6小鼠中,相对于其他品系,在正常血糖和低血糖时对高胰岛素血症的体内生理反应是中等的。C57 BL/6小鼠的胰岛素分泌与其他品系的小鼠相似,而与之相反,来自分离的胰岛的葡萄糖刺激的胰岛素分泌钝化。结论:在四个常用于遗传操作和糖代谢研究的近交系小鼠品系中存在品系依赖性差异。这些结果对于选择近交系小鼠研究葡萄糖代谢以及解释和设计实验具有重要意义。
OBJECTIVE—To characterize differences in whole-body glucose metabolism between commonly used inbred mouse strains. RESEARCH DESIGN AND METHODS—Hyperinsulinemic-euglycemic (∼8.5 mmol/l) and -hypoglycemic (∼3.0 mmol/l) clamps were done in catheterized, 5-h-fasted mice to assess insulin action and hypoglycemic counter-regulatory responsiveness. Hyperglycemic clamps (∼15 mmol/l) were done to assess insulin secretion and compared with results in perifused islets. RESULTS—Insulin action and hypoglycemic counter-regulatory and insulin secretory phenotypes varied considerably in four inbred mouse strains. In vivo insulin secretion was greatest in 129X1/Sv mice, but the counter-regulatory response to hypoglycemia was blunted. FVB/N mice in vivo showed no increase in glucose-stimulated insulin secretion, relative hepatic insulin resistance, and the highest counter-regulatory response to hypoglycemia. In DBA/2 mice, insulin action was lowest among the strains, and islets isolated had the greatest glucose-stimulated insulin secretion in vitro. In C57BL/6 mice, in vivo physiological responses to hyperinsulinemia at euglycemia and hypoglycemia were intermediate relative to other strains. Insulin secretion by C57BL/6 mice was similar to that in other strains in contrast to the blunted glucose-stimulated insulin secretion from isolated islets. CONCLUSIONS—Strain-dependent differences exist in four inbred mouse strains frequently used for genetic manipulation and study of glucose metabolism. These results are important for selecting inbred mice to study glucose metabolism and for interpreting and designing experiments.
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