Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment.
Induction of type-1 diabetes mellitus in laboratory rats by use of alloxan: route of administration, pitfalls, and insulin treatment.
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发表时间：
2004-06
影响因子：
0.8
通讯作者：
I. F. Federiuk;Heather M Casey;M. Quinn;M. D. Wood;W. Ward
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作者：
I. F. Federiuk;Heather M Casey;M. Quinn;M. D. Wood;W. Ward
药物引起的糖尿病（DM）的系统诱导和管理存在不确定性。问题包括药物的最佳给药途径、降低药物中毒和死亡率的方法、如何诱导 1 型糖尿病与 2 型糖尿病，以及如何管理大鼠的不稳定糖尿病。在尝试在 Sprague-Dawley 大鼠中诱导 1 型糖尿病时，我们仅当高血糖动物治疗后血酮浓度较高时才将其归类为 1 型糖尿病。我们发现多剂量四氧嘧啶导致的死亡率明显高于单剂量。单次高剂量（腹腔注射 200 毫克/公斤体重）是最佳治疗方法，导致 1 型糖尿病的发生率为 70%，死亡率仅为 10%。相反，相似剂量的静脉注射是有毒的。认真管理四氧嘧啶诱发的糖尿病对于避免大量胰岛素释放引起的严重低血糖和避免糖尿病酮症酸中毒至关重要。在此阶段，需要经常监测血糖并适当摄入碳水化合物和液体。对于长期管理，每日服用长效胰岛素（甘精胰岛素）似乎是安全有效的。速效胰岛素会迅速降低血糖浓度，必须谨慎使用。如果采取特定的预防措施，对实验室大鼠腹腔注射高剂量四氧嘧啶会导致与人类 1 型糖尿病非常相似的情况。
Uncertainties have existed regarding the systematic induction and management of drug-induced diabetes mellitus (DM). Issues have included the optimal route of administration of the drug, methods of reducing drug toxicosis and mortality, how to induce type-1 versus type-2 DM, and how to manage labile DM in rats. In attempting to induce type-1 DM in Sprague-Dawley rats, we classified hyperglycemic animals as having type-1 DM only if their post-treatment blood ketone concentration was high. We found that multiple doses of alloxan led to significantly higher mortality than did a single dose. A single high dose (200 mg/kg of body weight given intraperitoneally) was the best treatment and led to 70% incidence of type-1 DM and only 10% mortality. In contrast, intravenous administration of similar doses was toxic. Assiduous management of alloxan-induced DM is crucial to avoid severe hypoglycemia from massive insulin release and to avoid diabetic ketoacidosis. Frequent glucose monitoring and appropriate administration of carbohydrate and fluids is necessary during this stage. For long-term management, daily administration of long-acting insulin (glargine) appears to be safe and effective. Rapid-acting insulins reduce glucose concentration rapidly, and must be used with caution. If specific precautions are observed, intraperitoneal administration of high-dose alloxan to laboratory rats leads to a condition that closely resembles human type-1 DM.