Pederson R A, Campos R V, Buchan A M, Chisholm C B, Russell J C, Brown J C
Department of Physiology, University of British Columbia, Vancouver, Canada.
Int J Obes. 1991 Jul;15(7):461-70.
The 'fatty' Zucker and more recently the JCR:LA-cp 'corpulent' have been studied extensively as genetic models of the hyperinsulinemia, insulin resistance and abnormal fat metabolism of obesity. It has been hypothesized that an abnormal enteroinsular axis leading to hypersecretion of the insulin releasing hormone gastric inhibitory polypeptide (GIP) could contribute to the hyperinsulinemia of obesity, although this has been controversial. The present study was undertaken to compare the enteroinsular axis in fatty Zucker and JCR:LA-cp rats. The in vivo GIP and insulin responses to an oral glucose challenge, as well as glucose tolerance, were compared in lean and obese phenotypes of both strains as well as the sensitivity of the perfused pancreas to the secretagogues glucose, arginine and GIP. In addition, the effect of perfusate glucose concentration on the beta cell response to GIP was assessed in both strains. Tissue samples from the pancreas were taken for immunocytochemical analysis of comparative size and composition of pancreatic islets. Our results indicate that corpulent rats are hyperGIPemic when compared to fatty Zuckers and that hyperinsulinemia (both in vivo and in vitro) is more severe in the JCR:LA-cp than in the fatty Zucker, as is the degree of insulin resistance (as evidenced by glucose intolerance). Islets of corpulent rats were found to be larger than those of fa/fa rats as well as having a larger area occupied by beta cells. It was concluded that GIP may contribute to fasting hyperinsulinemia in the Zucker rat (as a result of a defective glucose threshold for the insulinotropic action of GIP), whereas the hyperGIPemia of the JCR:LA-cp rat may contribute to the massive nutrient-stimulated hyperinsulinemia observed in the male phenotype of this strain.
“肥胖型” Zucker大鼠以及最近的JCR:LA-cp “肥胖” 大鼠已被广泛研究，作为肥胖症高胰岛素血症、胰岛素抵抗和脂肪代谢异常的遗传模型。有人提出，异常的肠胰岛轴导致胰岛素释放激素胃抑制多肽（GIP）分泌过多，可能是肥胖症高胰岛素血症的原因，尽管这一点存在争议。本研究旨在比较肥胖型Zucker大鼠和JCR:LA-cp大鼠的肠胰岛轴。比较了这两个品系的瘦型和肥胖型表型对口服葡萄糖刺激的体内GIP和胰岛素反应以及葡萄糖耐量，以及灌注胰腺对促分泌剂葡萄糖、精氨酸和GIP的敏感性。此外，还评估了两个品系中灌注液葡萄糖浓度对β细胞对GIP反应的影响。采集胰腺组织样本，用于对胰岛的大小和组成进行免疫细胞化学分析。我们的结果表明，与肥胖型Zucker大鼠相比，肥胖型大鼠的GIP水平较高，并且JCR:LA-cp大鼠的高胰岛素血症（体内和体外）比肥胖型Zucker大鼠更严重，胰岛素抵抗程度也是如此（由葡萄糖耐量异常证明）。发现肥胖型大鼠的胰岛比fa/fa大鼠的胰岛更大，并且β细胞占据的面积更大。得出的结论是，GIP可能导致Zucker大鼠的空腹高胰岛素血症（由于GIP促胰岛素作用的葡萄糖阈值存在缺陷），而JCR:LA-cp大鼠的高GIP血症可能导致在该品系雄性表型中观察到的大量营养物质刺激的高胰岛素血症。
