Movassat J, Saulnier C, Serradas P, Portha B
Physiopathology of Nutrition Laboratory, CNRS URA 307, Université Paris 7-D. Diderot, France.
Diabetologia. 1997 Aug;40(8):916-25. doi: 10.1007/s001250050768.
In the endocrine pancreas of the GK rat, a genetic model of non-insulin-dependent diabetes mellitus (NIDDM), it is not clear whether the histopathological changes reported up to now are related to the pathogenesis of hyperglycaemia or whether they occur secondarily to metabolic alterations. Using GK rats from the Paris colony, our study chronicles for the first time the pathophysiologic changes that occur in the GK pancreas from the late fetal period (day 21.5) until adult age (18 weeks). As compared to Wistar controls, GK fetuses exhibited higher plasma glucose level, lower plasma insulin level and normal plasma glucagon level. Their pancreatic insulin content and the relative volume and the total mass of their beta cells were sharply decreased, representing only 23, 38 and 23% of control values, respectively. During the period from 4 days to 14 days after birth, GK neonates exhibited normal basal plasma glucose and glucagon levels despite decreased plasma insulin level. Their pancreatic insulin content represented only 31-40% of values found in the age-related control pancreases and their total beta-cell mass was only 35% on day 4, 30% on day 7 and 37% on day 14. The adult diabetic GK rats exhibited higher basal plasma glucose and insulin levels while their basal plasma glucagon level remained normal. Their pancreatic insulin content and the total beta-cell mass remained decreased, representing only 32% and 47% of control values, respectively. Moreover, the adult GK pancreases exhibited noticeable alteration in the architecture of the large islet subpopulation which displayed considerable fibrosis with clusters of beta cells widely separated from each other by strands of connective tissue. Concerning the development of alpha cells in the GK rats, their relative volume was found to be normal during fetal and early neonatal periods. It was found to be moderately decreased (representing 64-67% of corresponding control values) in 14-day-old neonates and adult GK rats. Our findings demonstrate that in the GK rat, the deficit of total beta-cell mass as observed in the adult animal is related to impaired beta-cell development. The restriction of the beta-cell mass must be considered as a primary and crucial event in the sequence leading to overt diabetes in this NIDDM model.
在非胰岛素依赖型糖尿病（NIDDM）的遗传模型GK大鼠的内分泌胰腺中，目前尚不清楚迄今为止报道的组织病理学变化是否与高血糖的发病机制有关，或者它们是否继发于代谢改变。本研究使用来自巴黎种群的GK大鼠，首次记录了从胎儿后期（第21.5天）到成年期（18周）GK胰腺中发生的病理生理变化。与Wistar对照相比，GK胎儿的血浆葡萄糖水平较高，血浆胰岛素水平较低，血浆胰高血糖素水平正常。其胰腺胰岛素含量以及β细胞的相对体积和总质量急剧下降，分别仅为对照值的23%、38%和23%。在出生后4天至14天期间，GK新生儿尽管血浆胰岛素水平下降，但基础血浆葡萄糖和胰高血糖素水平正常。其胰腺胰岛素含量仅为与年龄相关的对照胰腺中发现值的31%-40%，其β细胞总质量在第4天为35%，第7天为30%，第14天为37%。成年糖尿病GK大鼠的基础血浆葡萄糖和胰岛素水平较高，而其基础血浆胰高血糖素水平保持正常。其胰腺胰岛素含量和β细胞总质量仍然下降，分别仅为对照值的32%和47%。此外，成年GK胰腺在大胰岛亚群的结构上表现出明显改变，显示出相当程度的纤维化，β细胞簇被结缔组织束广泛分隔。关于GK大鼠中α细胞的发育，发现其在胎儿期和新生儿早期的相对体积正常。在14日龄新生儿和成年GK大鼠中发现其适度下降（占相应对照值的64%-67%）。我们的研究结果表明，在GK大鼠中，成年动物中观察到的β细胞总质量不足与β细胞发育受损有关。在这个NIDDM模型中，β细胞质量的限制必须被视为导致显性糖尿病的一系列事件中的一个主要且关键的事件。
