Scaglia L, Smith F E, Bonner-Weir S
E. P. Joslin Research Laboratories, Joslin Diabetes Center, Boston, Massachusetts 02215, USA.
Endocrinology. 1995 Dec;136(12):5461-8. doi: 10.1210/endo.136.12.7588296.
A significant reduction of beta cell mass has been described during the post partum period in the endocrine rat pancreas. We examined the mechanisms of this involution in Sprague Dawley rats by analyzing beta cell mass, beta cell replication, and beta cell size at end of pregnancy and 4 and 10 days after delivery. beta cell replication was significantly decreased at 4 days post partum but had returned back to nonpregnant levels by 10 days post partum. Similarly, beta cell size was significantly decreased at 4 and 10 days post partum as compared with the end of pregnancy, and at 10 days post partum was significantly decreased as compared with controls. At 4-6 days post partum, DNA fragmentation characteristic of apoptosis (programmed cell death) was detected in pancreatic islets, as assessed by in situ terminal deoxynucleotidyl transferase and nick translation assay. Only occasional cells were labeled with this assay in nonpregnant rats and at other time points after delivery. Condensed chromatin and apoptotic bodies, the morphological characteristics of apoptosis, were detected in beta cells of pancreatic islet at 3 and 4 days after delivery by electron microscopic analysis, confirming the occurrence of apoptosis in involuting islets. The expression of TRPM 2 and TGF beta 1, often enhanced in models of apoptosis, were studied during the post partum period by Northern blot analysis and immunohistochemistry. Levels of TRPM 2 gene and its protein, clusterin, were not different from controls; however, the TGF beta 1 gene and its protein expression were enhanced at 3 days post partum. Our study confirms the capability of beta cells to down-regulate their mass using the mechanisms of changes in rates of beta cell replication and of beta cell death, and changes in beta cell size to achieve homeostasis of the functional endocrine tissue.
在产后期间，已观察到内分泌大鼠胰腺中的β细胞量显著减少。我们通过分析妊娠末期、分娩后4天和10天的β细胞量、β细胞复制和β细胞大小，研究了斯普拉格-道利大鼠中这种退化的机制。产后4天β细胞复制显著减少，但产后10天已恢复到未怀孕水平。同样，与妊娠末期相比，产后4天和10天β细胞大小显著减小，且与对照组相比，产后10天β细胞大小也显著减小。通过原位末端脱氧核苷酸转移酶和缺口平移分析评估，在产后4 - 6天，胰岛中检测到凋亡（程序性细胞死亡）特有的DNA片段化。在未怀孕大鼠和分娩后的其他时间点，只有偶尔的细胞被这种分析标记。通过电子显微镜分析，在分娩后3天和4天的胰岛β细胞中检测到浓缩染色质和凋亡小体，这是凋亡的形态学特征，证实了退化胰岛中发生了凋亡。通过Northern印迹分析和免疫组织化学研究了产后期间TRPM 2和TGFβ1的表达，这两种蛋白在凋亡模型中常被增强。TRPM 2基因及其蛋白clusterin的水平与对照组无差异；然而，产后3天TGFβ1基因及其蛋白表达增强。我们的研究证实了β细胞有能力通过β细胞复制率、β细胞死亡以及β细胞大小的变化机制来下调其细胞量，以实现功能性内分泌组织的稳态。
