Russell J C, Ahuja S K, Manickavel V, Rajotte R V, Amy R M
Department of Surgery, University of Alberta, Edmonton, Canada.
Arteriosclerosis. 1987 Nov-Dec;7(6):620-6. doi: 10.1161/01.atv.7.6.620.
The LA/N-cp rat is, when homozygous for the cp gene, hyperphagous, hyperlipidemic, and corpulent. The corpulent males develop atherosclerotic disease and myocardial lesions while corpulent females and lean rats do not. The fasting plasma glucose concentrations of corpulent rats are in the normal range, but insulin concentrations are mildly elevated in corpulent females and markedly elevated in corpulent males. Glucose tolerance testing reveals a glucose intolerance in corpulent rats in the presence of very high insulin concentrations, and this deficiency is more severe in the male rats. Glucagon concentrations are higher in corpulent rats than lean rats at 3 months of age and decrease progressively with age. In contrast, glucagon concentrations increase with age in lean rats and are higher than those in corpulent rats at 9 months. The islets of Langerhans of corpulent rats exhibit marked hyperplasia that increases with age. The hyperplasia is less extreme in corpulent female rats. The abnormalities suggest that this strain of rats has an insulin resistance leading to impaired glucose tolerance and progressive pancreatic disturbance. This process may be related to an accompanying defect causing elevated concentrations of very low density lipoproteins and correlates with the development of atherosclerotic disease.
LA/N-cp大鼠在纯合cp基因时，表现为食欲亢进、高脂血症和肥胖。肥胖雄性大鼠会发展出动脉粥样硬化疾病和心肌病变，而肥胖雌性大鼠和瘦大鼠则不会。肥胖大鼠的空腹血糖浓度在正常范围内，但肥胖雌性大鼠的胰岛素浓度轻度升高，肥胖雄性大鼠的胰岛素浓度则显著升高。葡萄糖耐量测试显示，在胰岛素浓度非常高的情况下，肥胖大鼠存在葡萄糖不耐受，且这种缺陷在雄性大鼠中更为严重。在3个月大时，肥胖大鼠的胰高血糖素浓度高于瘦大鼠，并随年龄增长而逐渐降低。相比之下，瘦大鼠的胰高血糖素浓度随年龄增长而增加，在9个月时高于肥胖大鼠。肥胖大鼠的胰岛呈现出明显的增生，且随年龄增长而增加。肥胖雌性大鼠的增生程度较轻。这些异常表明，这种大鼠品系存在胰岛素抵抗，导致葡萄糖耐量受损和胰腺进行性紊乱。这个过程可能与导致极低密度脂蛋白浓度升高的伴随缺陷有关，并与动脉粥样硬化疾病的发展相关。
