Ogino T, Zhu M, Murakami T, Kuwajima M, Shima K
Department of Laboratory Medicine, University of Tokushima School of Medicine, Japan.
J Med Invest. 1998 Aug;45(1-4):103-10.
Wistar fatty rat, which has been established by transferring the fa gene of Zucker fatty rat to the Wistar Kyoto rat, has many features in common with human NIDDM. It exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance. It is unclear, however, whether a defect in the beta-cell proliferation is related to the onset of diabetes mellitus together with insulin resistance in this model rat. To determine this, we compared non-fasting plasma glucose levels, insulin content and beta-cell mass in the remnant pancreas of Wistar fatty rats with those in their diabetic-resistant lean counterparts after a 70% partial pancreatectomy. We also examined whether such a defect, if present, could be improved by either phlorizin or nicotinamide. We further investigated if there were any differences in these parameters between the phenotypically identical but genotypically different Wistar lean rats with a gene type of homogeneous Fa/Fa and that of heterogeneous Fa/fa. Male rats, 6 weeks of age, were allocated at random into two groups: 70% pancreatectomy (Px) and sham-pancreatectomy (sham). A sustained hyperglycemia was evident in the Px Wistar fatty rats after surgery, which was accompanied by a reduction of insulin content and beta-cell mass in the remnant pancreas. The changes in insulin content and beta-cell mass were unaffected by restoration of normoglycemia, induced by phlorizin injection. The administration of nicotinamide partially ameliorated the sustained hyperglycemia by a slight but not significant increase in beta-cell mass. No discernible difference in the above parameters was observed between the Wistar lean rats with Fa/Fa and those with Fa/fa. These findings suggest that Wistar fatty rats have a poor capacity for proliferation of pancreatic beta-cells, which causes the onset of overt diabetes along with insulin resistance due to extreme obesity.
通过将Zucker肥胖大鼠的fa基因转移到Wistar京都大鼠而培育出的Wistar肥胖大鼠，具有许多与人类非胰岛素依赖型糖尿病（NIDDM）相同的特征。它表现为高血糖性肥胖，伴有高胰岛素血症和胰岛素抵抗。然而，在这种模型大鼠中，β细胞增殖缺陷是否与糖尿病的发生以及胰岛素抵抗有关尚不清楚。为了确定这一点，我们比较了70%胰腺部分切除术后Wistar肥胖大鼠与其抗糖尿病的瘦型对照大鼠残余胰腺中的非空腹血糖水平、胰岛素含量和β细胞质量。我们还研究了如果存在这种缺陷，是否可以通过根皮苷或烟酰胺来改善。我们进一步研究了表型相同但基因型不同的纯合Fa/Fa和杂合Fa/fa的Wistar瘦大鼠在这些参数上是否存在差异。6周龄的雄性大鼠被随机分为两组：70%胰腺切除术（Px）组和假胰腺切除术（sham）组。手术后，Px组Wistar肥胖大鼠出现持续高血糖，同时残余胰腺中的胰岛素含量和β细胞质量降低。根皮苷注射诱导的血糖正常化并未影响胰岛素含量和β细胞质量的变化。烟酰胺的给药通过轻微但不显著增加β细胞质量，部分改善了持续高血糖。在Fa/Fa和Fa/fa的Wistar瘦大鼠之间，未观察到上述参数有明显差异。这些发现表明，Wistar肥胖大鼠的胰腺β细胞增殖能力较差，这导致了明显的糖尿病发作以及由于极度肥胖引起的胰岛素抵抗。
