Larsen Marianne Olholm, Rolin Bidda, Wilken Michael, Carr Richard David, Svendsen Ove
Department of Pharmacological Research I, Novo Nordisk A/S, Bagsvaerd, Denmark.
Ann N Y Acad Sci. 2002 Jun;967:414-23. doi: 10.1111/j.1749-6632.2002.tb04297.x.
High-fat diet and obesity are known to be of major importance for development of type 2 diabetes in humans. High-fat feeding can induce syndromes of glucose intolerance and/or insulin resistance in several species, and the Göttingen minipig might be a useful model for studying the effect of dietary high-fat intake and obesity on glucose homeostasis and the susceptibility to diabetes. The present study was designed as a pilot study to investigate the effects of obesity caused by high-fat high-energy feeding on oral and intravenous glucose tolerance. Male Göttingen minipigs were fed a control diet (CD) or a high-fat high-energy diet (HFD) for 3 months. Body weight (32.6 +/- 2.4 kg vs. 24.9 +/- 0.5 kg, p < 0.001) and total (13.2 +/- 3.2% vs. 6.1 +/- 0.5%, p = 0.002) and truncal (11.0 +/- 3.9% vs. 1.8 +/- 1.1%, p = 0.001) fat percent were increased significantly, whereas relative lean body mass was decreased (84.8 +/- 3.3% vs. 91.9 +/- 0.5%, p = 0.002) in the HFD group compared to CD. Fasting plasma glucose (4.3 +/- 0.4 mM vs. 3.6 +/- 0.3 mM, p = 0.023) and insulin (80 +/- 23 pM vs. 23 +/- 21 pM, p = 0.012) were increased in the HFD group compared to CD, but oral glucose tolerance was not significantly changed. Insulin responses to intravenous glucose were increased (6741 +/- 2538 vs. 3938 +/- 771 pM 3 min, p = 0.050), while glucose clearance was not changed by HFD vs. CD, thus indicating insulin resistance. In conclusion, changes in body weight and composition, resulting in minor abnormalities in glucose tolerance and insulin sensitivity, characterized by slight hyperglycemia and compensatory hyperinsulinemia, can be induced in the male Göttingen minipig by high-fat high-energy feeding for 3 months. This approach seems to be an interesting and promising method for establishment of a nonrodent model of insulin resistance or type 2 diabetes.
众所周知，高脂饮食和肥胖对于人类2型糖尿病的发展至关重要。高脂喂养可在多个物种中诱发葡萄糖不耐受和/或胰岛素抵抗综合征，而哥廷根小型猪可能是研究饮食中高脂肪摄入和肥胖对葡萄糖稳态及糖尿病易感性影响的有用模型。本研究设计为一项试点研究，旨在调查高脂高能量喂养导致的肥胖对口服和静脉葡萄糖耐量的影响。雄性哥廷根小型猪被喂食对照饮食（CD）或高脂高能量饮食（HFD）3个月。与CD组相比，HFD组的体重（32.6±2.4 kg对24.9±0.5 kg，p<0.001）、总体脂肪百分比（13.2±3.2%对6.1±0.5%，p = 0.002）和躯干脂肪百分比（11.0±3.9%对1.8±1.1%，p = 0.001）显著增加，而相对瘦体重降低（84.8±3.3%对91.9±0.5%，p = 0.002）。与CD组相比，HFD组的空腹血糖（4.3±0.4 mM对3.6±0.3 mM，p = 0.023）和胰岛素（80±23 pM对23±21 pM，p = 0.012）升高，但口服葡萄糖耐量无显著变化。HFD组对静脉注射葡萄糖的胰岛素反应增加（6741±2538对3938±771 pM 3分钟，p = 0.050），而与CD组相比，HFD组的葡萄糖清除率未改变，因此表明存在胰岛素抵抗。总之，通过3个月的高脂高能量喂养，可在雄性哥廷根小型猪中诱导体重和组成的变化，导致葡萄糖耐量和胰岛素敏感性出现轻微异常，表现为轻度高血糖和代偿性高胰岛素血症。这种方法似乎是建立非啮齿类胰岛素抵抗或2型糖尿病模型的一种有趣且有前景的方法。
