β-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy
β-cell proliferation and apoptosis in the developing normal human pancreas and in hyperinsulinism of infancy
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DOI：
10.2337/diabetes.49.8.1325
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发表时间：
2000-08-01
期刊：
影响因子：
7.7
通讯作者：
Glaser, B
中科院分区：
文献类型：
--
作者：
Kassem, SA;Ariel, I;Glaser, B
婴儿期高胰岛素血症（HI），也称为婴儿期持续性高胰岛素血症性低血糖，是一种罕见的遗传性疾病，发生率约为1/50，000。在组织学上，来自HI患者的胰腺可分为2个主要组。在第一个弥漫性HI中，β细胞分布与正常新生儿胰腺中所见相似，而在第二个局灶性HI中，存在β细胞腺瘤样增生的离散区域。在大多数患者中，疾病的临床过程表明p-cen功能的缓慢进行性丧失。使用双重免疫染色，我们研究了在正常人胰腺和弥漫性和局灶性HI患者胰腺的发展过程中进行增殖和凋亡的β细胞的比例。在对照样本中，我们的研究结果显示β细胞增殖从妊娠17周和32周之间的3.2 +/- 0.5%逐渐降低到6个月后的0.13 +/- 0.08%。相比之下，细胞凋亡的频率在妊娠17-32周较低（0.6 +/- 0.2%），在围产期升高（1.3 +/- 0.3%），6个月后再次降低（0.08 +/- 0.3%）。HI β细胞显示增殖频率增加，局灶性病变显示特别高的水平。类似地，HI中凋亡细胞的比例增加，尽管这仅在3个月龄后达到统计学显著性。总之，我们证明了新生儿期的胰岛重塑可能主要是由于那时发生的p-cen凋亡波。在HI中，我们发现持续增加的β细胞增殖和凋亡提供了一种可能的机制来解释弥漫性疾病中所见的组织学图像。临床上在这些患者中观察到的胰岛素分泌缓慢进行性减少表明，这些现象的净效应可能是β细胞质量损失。
Hyperinsulinism of infancy (HI), also known as persistent hyperinsulinemic hypoglycemia of infancy, is a rare genetic disorder that occurs in similar to 1 of 50,000 live births. Histologically, pancreases from HI patients can be divided into 2 major groups. In the first, diffuse HI, beta-cell distribution is similar to that seen in normal neonatal pancreas, whereas in the second, focal HI, there is a discrete region of beta-cell adenomatous hyperplasia. In most patients, the clinical course of the disease suggests a slow progressive loss of p-cen function. Using double immunostaining, we examined the proportion of beta-cells undergoing proliferation and apoptosis during the development of the normal human pancreas and in pancreases from diffuse and focal HI patients. In the control samples, our findings show a progressive decrease in beta-cell proliferation from 3.2 +/- 0.5% between 17 and 32 weeks of gestation to 0.13 +/- 0.08% after 6 months of age. In contrast, frequency of apoptosis is low (0.6 +/- 0.2%) in weeks 17-32 of gestation, elevated (1.3 +/- 0.3%) during the perinatal period, and again low (0.08 +/- 0.3%) after 6 months of age. HI beta-cells showed an increased frequency of proliferation, with focal lesions showing particularly high levels. Similarly, the proportion of apoptotic cells was increased in HI, although this reached statistical significance only after 3 months of age. In conclusion, we demonstrated that islet remodeling normally seen in the neonatal period may be primarily due to a wave of p-cen apoptosis that occurs at that time. In HI, our findings of persistently increased beta-cell proliferation and apoptosis provide a possible mechanism to explain the histologic picture seen in diffuse disease. The slow progressive decrease in insulin secretion seen clinically in these patients suggests that the net effect of these phenomena may be loss of beta-cell mass.