Streptozotocin is equally diabetogenic whether administered to fed or fasted mice.
Streptozotocin is equally diabetogenic whether administered to fed or fasted mice.
复制标题
DOI：
10.1177/0023677213489548
复制
发表时间：
2013-10
影响因子：
2.4
通讯作者：
Evans-Molina C
中科院分区：
文献类型：
--
作者：
Chaudhry ZZ;Morris DL;Moss DR;Sims EK;Chiong Y;Kono T;Evans-Molina C
链脲佐菌素（STZ）是一种选择性胰腺β细胞毒素，用于在啮齿动物模型中产生实验性高血糖。几种实验室动物方案表明，STZ应给予禁食的啮齿动物，以最大限度地减少STZ和葡萄糖之间对β细胞上低亲和力GLUT 2转运蛋白的竞争。然而，多次低剂量（MLD）-STZ给药的致糖尿病效应是否会因禁食而增强尚未得到解决。鉴于反复禁食可导致小鼠过度代谢应激，我们比较了MLD-STZ注射（每天50 mg/kg体重，持续5天）在NOD/SCID/γ链缺失和C57 BL/6 J小鼠中诱导实验性高血糖症的疗效，这些小鼠在STZ给药前自由进食（STZ-进食）或禁食6小时（STZ-禁食）。在开始MLD-STZ方案后10天，STZ-进食和STZ-禁食小鼠的葡萄糖耐量均显著差于媒介物处理的对照小鼠。在C57 BL/6 J小鼠中，MLD-STZ后20天，STZ-进食和STZ-禁食小鼠之间的空腹葡萄糖水平、血清胰岛素水平、β细胞质量和腹膜内葡萄糖耐量试验（IPGTT）期间的葡萄糖处置无法区分。葡萄糖不耐受表型持续20周后，无论C57 BL/6 J小鼠是否在STZ注射时进食或禁食。然而，STZ禁食的C57 BL/6 J小鼠在完成MLD-STZ方案所需的重复禁食/再喂养期间经历了显著的体重减轻。总之，使用MLD-STZ方案可以实现实验性高血糖的诱导，而无需重复禁食，这有可能导致实验室小鼠的代谢应激。
Streptozotocin (STZ) is a selective pancreatic β cell toxin used to generate experimental hyperglycemia in rodent models. Several laboratory animal protocols suggest that STZ be administered to fasted rodents to minimize competition between STZ and glucose for low affinity GLUT2 transporters on β cells. However, whether the diabetogenic effects of multiple low dose (MLD)-STZ administration are enhanced by fasting has not been addressed. Given that repeated bouts of fasting can cause undue metabolic stress in mice, we compared the efficacy of MLD-STZ injections (50 mg/kg body weight daily for 5 days) to induce experimental hyperglycemia in both NOD/SCID/γchainnull and C57BL/6J mice that were either ad libitum fed (STZ-Fed) or that had been fasted for 6 h (STZ-Fasted) prior to the time of STZ administration. Both STZ-Fed and STZ-Fasted mice had significantly worse glucose tolerance than vehicle-treated control mice 10 days after initiation of the MLD-STZ regimen. In C57BL/6J mice, fasting glucose levels, serum insulin levels, β cell mass, and glucose disposal during intraperitoneal glucose tolerance tests (IPGTTs) were indistinguishable between STZ-Fed and STZ-Fasted mice 20 days after MLD-STZ. The glucose intolerant phenotypes persisted for 20 weeks thereafter, irrespective of whether C57BL/6J mice were fed or fasted at the time of STZ injections. However, STZ-Fasted C57BL/6J mice experienced significant weight loss during the repeated bouts of fasting/re-feeding that were required to complete the MLD-STZ protocol. In summary, induction of experimental hyperglycemia can be achieved using the MLD-STZ protocol without repeated bouts of fasting, which have the potential to cause metabolic stress in laboratory mice.
登录
查看更多内容
影响因子：
7.7
作者：
SCHNEDL, WJ;FERBER, S;NEWGARD, CB
通讯作者：
NEWGARD, CB
影响因子：
158.5
作者：
MOERTEL, CG;LEFKOPOULO, M;KLAASSEN, D
通讯作者：
KLAASSEN, D
影响因子：
4.1
作者：
Konrad, RJ;Mikolaenko, I;Kudlow, JE
通讯作者：
Kudlow, JE
影响因子：
15.9
作者：
Song, Benbo;Scheuner, Donalyn;Kaufman, Randal J.
通讯作者：
Kaufman, Randal J.
DOI：
10.1073/pnas.79.2.630
发表时间：
1982-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LEITER, EH
通讯作者：
LEITER, EH