Department of Clinical Pharmaceutics & Pharmacy Practice, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Biol Pharm Bull. 2010;33(6):988-92. doi: 10.1248/bpb.33.988.
Selective breeding was used to isolate hyperglycemic (ddY-H) or normoglycemic (ddY-L) mice that had been induced by fasting and refeeding. Serum glucose levels 12 h after 48 h-fasting were high in male ddY-H mice, but relatively low in male ddY-L mice compared with control ddY mice. Glucose tolerance was impaired in ddY-H mice maintained with standard chow pellets ad libitum at 12 weeks of age, and serum glucose and insulin levels were significantly increased after overnight fasting at 15 weeks of age. ddY-L mice indices did not differ from ddY mice indices, suggesting that insulin resistance is spontaneously induced in ddY-H mice. Increases in urinary excretion and urinary sugar accompanied by increased body mass were observed in all ddY-H mice, but not in ddY or ddY-L mice, at 27 weeks of age, indicating the induction of diabetic symptoms. Cross-mating between ddY-H and ddY-L mice was used to certify the genetic involvement in impaired glucose tolerance. This was not induced in mice born from male ddY-H and female ddY-L mice, or from female ddY-H and male ddY-L mice. In conclusion, ddY-H mice are a useful diabetic mouse model that show spontaneously induced insulin resistance followed by diabetic symptoms that are maintained by standard chow pellets. Their characteristics are recessively inherited, and ddY-L mice are an appropriate choice as control mice.
通过选择性繁殖，我们分离出了空腹再喂食诱导的高血糖（ddY-H）或正常血糖（ddY-L）小鼠。雄性 ddY-H 小鼠在禁食 48 小时后 12 小时的血清葡萄糖水平较高，而雄性 ddY-L 小鼠的血清葡萄糖水平相对较低，与对照 ddY 小鼠相比。在 12 周龄时，给予 ddY-H 小鼠标准的自由进食饲料，它们的葡萄糖耐量受损，而在 15 周龄时，经过一夜禁食后，它们的血清葡萄糖和胰岛素水平显著升高。ddY-L 小鼠的指标与 ddY 小鼠的指标没有差异，这表明胰岛素抵抗是 ddY-H 小鼠自发诱导的。在 27 周龄时，所有 ddY-H 小鼠都出现了尿排泄和尿糖增加，伴随着体重增加，而 ddY 或 ddY-L 小鼠则没有，这表明糖尿病症状的诱导。ddY-H 和 ddY-L 小鼠之间的交叉交配用于证明葡萄糖耐量受损与遗传有关。在雄性 ddY-H 和雌性 ddY-L 小鼠或雌性 ddY-H 和雄性 ddY-L 小鼠所生的小鼠中，没有诱导出这种情况。总之，ddY-H 小鼠是一种有用的糖尿病小鼠模型，它们表现出自发性诱导的胰岛素抵抗，随后出现维持在标准饲料下的糖尿病症状。它们的特征是隐性遗传的，而 ddY-L 小鼠是合适的对照小鼠。
