Hashimoto H, Arai T, Mori A, Kawai K, Hikishima K, Ohnishi Y, Eto T, Ito M, Hioki K, Suzuki R, Ohsugi M, Saito M, Ueyama Y, Okano H, Yamauchi T, Kubota N, Ueki K, Tobe K, Tamaoki N, Kadowaki T, Kosaka K
Central Institute for Experimental Animals, Kawasaki-shi, Kanagawa, Japan.
Exp Clin Endocrinol Diabetes. 2009 Nov;117(10):577-86. doi: 10.1055/s-0029-1225352. Epub 2009 Jul 23.
Current Japanese and American diets and Japanese diet immediately after the War were converted to laboratory animal diets. As a result, current laboratory animal diet (CA-1, CLEA) unexpectedly resembled the diet of Japanese after the War. This is considered to result in an under-evaluation of diabetes research using laboratory animals at present. Therefore, changes in insulin signals caused by current Japanese and American diets were examined using IRS-2 deficient mice ( IRS2(-/-) mice) and mechanisms of aggravation of type 2 diabetes due to modern diets were examined. IRS2(-/-) mice at 6 weeks of age were divided into three groups: Japanese diet (Jd) group, American diet (Ad) group and CA-1 diet [regular diet (Rd)] group. Each diet was given to the dams from 7 days before delivery. When the IRS2(-/-) mice reached 6 weeks of age, the glucose tolerance test (GTT), insulin tolerance test (ITT) and organ sampling were performed. The sampled organs and white adipose tissue were used for analysis of RNA, enzyme activity and tissues. In GTT and ITT, the Ad group showed worse glucose tolerance and insulin resistance than the Rd group. Impaired glucose tolerance of the Jd group was the same as that of the Rd group, but insulin resistance was worse than in the Rd group. These results were caused an increase in fat accumulation and adipocytes in the peritoneal cavity by lipogenic enzyme activity in the liver and muscle, and the increase in TNFalpha of hypertrophic adipocyte origin further aggravated insulin resistance and the increase in resistin also aggravated the impaired glucose tolerance, leading to aggravation of type 2 diabetes. The Japanese and American diets given to the IRS2(-/-) mice, which we developed, showed abnormal findings in some IRS2(-/-) mice but inhibited excessive reactions of insulin signals as diets used in ordinary nutritional management.
当前的日本和美国饮食以及战后日本的饮食都被转化为实验动物饮食。结果，当前的实验动物饮食（CA - 1，CLEA）意外地与战后日本人的饮食相似。这被认为导致了目前对使用实验动物进行糖尿病研究的评估不足。因此，使用胰岛素受体底物2缺陷小鼠（IRS2(-/-)小鼠）研究了当前日本和美国饮食引起的胰岛素信号变化，并研究了现代饮食导致2型糖尿病加重的机制。6周龄的IRS2(-/-)小鼠被分为三组：日本饮食（Jd）组、美国饮食（Ad）组和CA - 1饮食[常规饮食（Rd）]组。从分娩前7天开始，给母鼠喂食每种饮食。当IRS2(-/-)小鼠达到6周龄时，进行葡萄糖耐量试验（GTT）、胰岛素耐量试验（ITT）和器官取样。采集的器官和白色脂肪组织用于RNA、酶活性和组织分析。在GTT和ITT中，Ad组的葡萄糖耐量和胰岛素抵抗比Rd组更差。Jd组的葡萄糖耐量受损程度与Rd组相同，但胰岛素抵抗比Rd组更严重。这些结果是由肝脏和肌肉中脂肪生成酶活性导致腹腔内脂肪堆积和脂肪细胞增加引起的，肥大脂肪细胞来源的肿瘤坏死因子α增加进一步加重了胰岛素抵抗，抵抗素增加也加重了葡萄糖耐量受损，导致2型糖尿病加重。我们给IRS2(-/-)小鼠喂食的日本和美国饮食，在一些IRS2(-/-)小鼠中显示出异常结果，但作为普通营养管理中使用的饮食，抑制了胰岛素信号的过度反应。
