Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice.
Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice.
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作者：
Lee Y;Wang MY;Du XQ;Charron MJ;Unger RH
确定胰高血糖素在未经治疗的胰岛素缺乏症代谢表型中的作用。我们比较了胰高血糖素受体缺失（Gcgr−/−）小鼠和野生型（Gcgr+/+）对照小鼠在同等破坏β细胞后的相关临床和代谢参数。我们使用了双倍剂量的链脲佐菌素来最大化β细胞的破坏。Gcgr+/+小鼠变得高血糖（>500 mg/dL）、高酮血症、多尿和恶病质，并且必须在6周后处死。尽管Gcgr−/−小鼠的β细胞破坏相当，但没有出现上述糖尿病的临床或实验室表现。有明显的α-细胞增生和高胰高血糖素血症（> 1，200 pg/mL），但与患有糖尿病的Gcgr+/+小鼠相比，肝脏磷酸化cAMP反应元件结合蛋白和磷酸烯醇式丙酮酸羧激酶mRNA显著降低-证据表明胰高血糖素作用已被有效阻断。空腹血糖水平和口服及腹腔内葡萄糖耐量试验均正常。空腹和非空腹游离脂肪酸水平和非空腹β-羟基丁酸水平均较低。我们的结论是，阻断胰高血糖素的作用，防止致命的代谢和临床紊乱的1型糖尿病小鼠。
To determine the role of glucagon action in the metabolic phenotype of untreated insulin deficiency. We compared pertinent clinical and metabolic parameters in glucagon receptor-null (Gcgr−/−) mice and wild-type (Gcgr+/+) controls after equivalent destruction of β-cells. We used a double dose of streptozotocin to maximize β-cell destruction. Gcgr+/+ mice became hyperglycemic (>500 mg/dL), hyperketonemic, polyuric, and cachectic and had to be killed after 6 weeks. Despite comparable β-cell destruction in Gcgr−/− mice, none of the foregoing clinical or laboratory manifestations of diabetes appeared. There was marked α-cell hyperplasia and hyperglucagonemia (∼1,200 pg/mL), but hepatic phosphorylated cAMP response element binding protein and phosphoenolpyruvate carboxykinase mRNA were profoundly reduced compared with Gcgr+/+ mice with diabetes—evidence that glucagon action had been effectively blocked. Fasting glucose levels and oral and intraperitoneal glucose tolerance tests were normal. Both fasting and nonfasting free fatty acid levels and nonfasting β-hydroxy butyrate levels were lower. We conclude that blocking glucagon action prevents the deadly metabolic and clinical derangements of type 1 diabetic mice.
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影响因子：
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作者：
JOHNSON, DG;GOEBEL, CU;TRIVEDI, D
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TRIVEDI, D
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BAJORUNAS, DR;FORTNER, JG;JASPAN, JB
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BEALE, E;ANDREONE, T;GRANNER, D
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GRANNER, D
影响因子：
7.7
作者：
Parker, JC;McPherson, RK;Treadway, JL
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Treadway, JL