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Development of a Nongenetic Mouse Model of Type 2 Diabetes

机译:2型糖尿病的非遗传小鼠模型的发展。

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Insulin resistance and loss ofβ-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 reducedβ-cell mass.
机译:胰岛素抵抗和β细胞量减少导致2型糖尿病(T2D)。这项研究的目的是生成T2D的非遗传小鼠模型。将96例6个月大的C57BL / 6N男性分为12组中的1组,其中包括(1)低脂饮食(LFD;低脂对照; LFC),(2)LFD,腹腔内麻醉1 ip。 40 mg / kg BW链脲佐菌素(STZ)注射,(3),(4),(5),(6)LFD,分别连续2天,3、4或5次STZ注射,(7)高脂饮食(HFD),(8)连续1天注射STZ的HFD,(9),(10),(11),(12)连续2天,3、4或5次STZ注射的HFD。 4周后,与HFC相比,至少两次STZ注射的HFD小鼠血清胰岛素水平降低。食用HFD并接受2、3或4次STZ注射的小鼠的糖耐量受损。无论STZ处理如何,HFD小鼠的胰岛素敏感性均低于LFD小鼠。胰岛质量不受饮食影响,但在接受3次STZ注射的小鼠中,胰岛质量减少了50%。 HFD和三剂40μmg/ kg STZ注射剂的组合可诱导出具有T2D代谢特征的模型,包括外周胰岛素抵抗和β细胞量减少。

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