Movassat J, Saulnier C, Portha B
Lab. Physiopathology of Nutrition, CNRS URA 307, University D. Diderot/Paris 7.
Diabete Metab. 1995 Dec;21(5):365-70.
It is unclear whether reported histopathological changes in the endocrine pancreas of the GK rat (a spontaneous model of non-insulin-dependent diabetes) are related to the pathogenesis of hyperglycaemia or occur secondarily to metabolic alterations. We found that total pancreatic insulin stores in GK rats from the Paris colony were depleted by 62% (p < 0.01) in adult (4-month-old) overtly hyperglycaemic animals compared to those of normal Wistar control rats, and that beta-cell mass in GK pancreata was decreased to a similar extent (51%, p < 0.05). This indicates that decreased in vivo and in vitro insulin secretory response to glucose in GK rats could be due not only to impaired stimulus-secretion coupling for glucose in their beta cells but also to a reduced number of beta cells. Reduced total beta-cell mass in adult GK rats was associated with a noticeable alteration in the architecture of a subpopulation of islets: only large islets displayed signs of disorganization of the mantle-core relationship due to prominent fibrosis, with clusters of beta cells widely separated by strands of connective tissue. Our study also provides a first record of the pathophysiologic changes occurring in the GK rat from the neonatal period. Four-day-old GK pups demonstrated normal basal glycaemia compared to Wistar rats of the same age. GK islets displayed a well-preserved architecture, with normal staining of beta cells and no fibrosis. However, their total pancreatic insulin stores and total beta-cell mass were significantly lower [59% (p < 0.01) and 64% (p < 0.05) respectively] than those of controls. These data indicate that a reduction in islet tissue clearly predates the onset of diabetes (hyperglycaemia). Therefore, a reduction of total beta-cell mass should be considered as a primary feature in the pathological sequence leading to diabetes in GK rats, at least in those originating from the Paris colony.
尚不清楚GK大鼠（非胰岛素依赖型糖尿病的自发模型）内分泌胰腺中报道的组织病理学变化是与高血糖的发病机制相关，还是继发于代谢改变。我们发现，与正常Wistar对照大鼠相比，来自巴黎种群的成年（4月龄）明显高血糖的GK大鼠的胰腺胰岛素总储存量减少了62%（p<0.01），并且GK胰腺中的β细胞量也有类似程度的减少（51%，p<0.05）。这表明GK大鼠体内和体外对葡萄糖的胰岛素分泌反应降低，不仅可能是由于其β细胞中葡萄糖刺激-分泌偶联受损，还可能是由于β细胞数量减少。成年GK大鼠β细胞总量减少与胰岛亚群结构的明显改变有关：只有大胰岛由于明显的纤维化而显示出被膜-核心关系紊乱的迹象，β细胞簇被结缔组织束广泛分隔。我们的研究还首次记录了GK大鼠从新生儿期开始发生的病理生理变化。与同龄的Wistar大鼠相比，4日龄的GK幼崽基础血糖正常。GK胰岛结构保存良好，β细胞染色正常，无纤维化。然而，它们的胰腺胰岛素总储存量和β细胞总量显著低于对照组[分别为59%（p<0.01）和64%（p<0.05）]。这些数据表明，胰岛组织的减少明显早于糖尿病（高血糖）的发生。因此，至少在来自巴黎种群的GK大鼠中，β细胞总量的减少应被视为导致糖尿病的病理过程中的主要特征。
