Development of a nongenetic mouse model of type 2 diabetes.
Development of a nongenetic mouse model of type 2 diabetes.
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DOI：
10.1155/2011/416254
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发表时间：
2011
影响因子：
--
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Gilbert ER;Fu Z;Liu D
胰岛素抵抗和β细胞团的损失导致2型糖尿病（T2D）。本研究的目的是建立非遗传性小鼠T2D模型。选取96只6月龄C57BL/6N雄性小鼠，分为12组：(1)低脂饮食组（LFD），低脂对照组（LFC），(2)低脂饮食组（LFD）注射1磅/ 40 mg/kg BW链脲佐菌素（STZ），(3),(4),(5),(6)高脂饮食组（HFD），(8)高脂饮食组（HFD）注射STZ 1次，(9),(10),(11),（12）高脂饮食组（HFD）注射STZ 2次，(3),(4),(6)连续注射STZ 2次，（10），（11），（12）HFD连续注射STZ 2次，3次，4次或5次。4周后，与HFC相比，注射至少2次STZ的HFD小鼠血清胰岛素水平降低。摄入HFD并接受2、3或4次STZ注射的小鼠葡萄糖耐量受损。无论STZ治疗方式如何，HFD小鼠的胰岛素敏感性均低于LFD小鼠。胰岛质量不受饮食的影响，但在接受3次STZ注射的小鼠中，胰岛质量减少了50%。HFD联合三次40 mg/kg STZ注射可诱导具有T2D代谢特征的模型，包括外周胰岛素抵抗和β细胞质量减少。
Insulin resistance and loss of β-cell mass cause Type 2 diabetes (T2D). The objective of this study was to generate a nongenetic mouse model of T2D. Ninety-six 6-month-old C57BL/6N males were assigned to 1 of 12 groups including (1) low-fat diet (LFD; low-fat control; LFC), (2) LFD with 1 i.p. 40 mg/kg BW streptozotocin (STZ) injection, (3), (4), (5), (6) LFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively, (7) high-fat diet (HFD), (8) HFD with 1 STZ injection, (9), (10), (11), (12) HFD with 2, 3, 4, or 5 STZ injections on consecutive days, respectively. After 4 weeks, serum insulin levels were reduced in HFD mice administered at least 2 STZ injections as compared with HFC. Glucose tolerance was impaired in mice that consumed HFD and received 2, 3, or 4 injections of STZ. Insulin sensitivity in HFD mice was lower than that of LFD mice, regardless of STZ treatment. Islet mass was not affected by diet but was reduced by 50% in mice that received 3 STZ injections. The combination of HFD and three 40 mg/kg STZ injections induced a model with metabolic characteristics of T2D, including peripheral insulin resistance and reduced β-cell mass.
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