Shi Weibin, Li Jing, Bao Kelly, Chen Mei-Hua, Liu Zhenqi
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA 22908, USA.
Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Biomedicines. 2022 Jun 16;10(6):1429. doi: 10.3390/biomedicines10061429.
and mice are two animal models extensively used for atherosclerosis research. We previously reported that mice on certain genetic backgrounds, including C3H/HeJ (C3H), develop type 2 diabetes when fed a Western diet. We sought to characterize diabetes-related traits in C3H- mice through comparing with C3H- mice. On a chow diet, mice had lower plasma total and non-HDL cholesterol levels but higher HDL levels than mice. Fasting plasma glucose was much lower in than mice (male: 122.5 ± 5.9 vs. 229.4 ± 17.5 mg/dL; female: 144.1 ± 12.4 vs. 232.7 ± 6.4 mg/dL). When fed a Western diet, and mice developed severe hypercholesterolemia and also hyperglycemia with fasting plasma glucose levels exceeding 250 mg/dL. Both knockouts had similar non-HDL cholesterol and triglyceride levels, and their fasting glucose levels were also similar. Male mice exhibited greater glucose tolerance and insulin sensitivity compared to their counterpart. Female mice showed similar glucose tolerance and insulin sensitivity though mice had higher non-fasting glucose levels. Male and mice developed moderate obesity on the Western diet, but female mice did not. These results indicate that the Western diet and ensuing hyperlipidemia lead to the development of type 2 diabetes, irrespective of underlying genetic causes.
小鼠是广泛用于动脉粥样硬化研究的两种动物模型。我们之前报道过，某些遗传背景的小鼠，包括C3H/HeJ（C3H），在喂食西式饮食时会患2型糖尿病。我们试图通过与C3H小鼠比较来表征C3H小鼠与糖尿病相关的特征。在普通饮食中，C3H小鼠的血浆总胆固醇和非高密度脂蛋白胆固醇水平较低，但高密度脂蛋白水平高于C3H小鼠。C3H小鼠的空腹血糖比C3H小鼠低得多（雄性：122.5±5.9 vs. 229.4±17.5 mg/dL；雌性：144.1±12.4 vs. 232.7±6.4 mg/dL）。当喂食西式饮食时，C3H和C3H小鼠都出现了严重的高胆固醇血症，并且空腹血糖水平超过250 mg/dL时也出现了高血糖。两种基因敲除小鼠的非高密度脂蛋白胆固醇和甘油三酯水平相似，它们的空腹血糖水平也相似。与C3H小鼠相比，雄性C3H小鼠表现出更好的葡萄糖耐量和胰岛素敏感性。雌性C3H小鼠的葡萄糖耐量和胰岛素敏感性相似，尽管C3H小鼠的非空腹血糖水平较高。在西式饮食中，雄性C3H和C3H小鼠出现了中度肥胖，但雌性小鼠没有。这些结果表明，西式饮食和随之而来的高脂血症会导致2型糖尿病的发生，而与潜在的遗传原因无关。
