FUNCTIONAL MATURATION AND PROLIFERATION OF FETAL PANCREATIC BETA-CELLS
FUNCTIONAL MATURATION AND PROLIFERATION OF FETAL PANCREATIC BETA-CELLS
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DOI：
10.2337/diab.40.2.s89
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发表时间：
1991-12-01
期刊：
影响因子：
7.7
通讯作者：
SWENNE, I
中科院分区：
文献类型：
--
作者：
HELLERSTROM, C;SWENNE, I
本文综述了胎儿β细胞中刺激-分泌偶联成熟和DNA复制调控的一些关键方面。在胎儿期，β细胞对葡萄糖的胰岛素反应较差，尽管它对其他几种非营养刺激有反应。然而，长期暴露于超过基础水平的葡萄糖可以诱导刺激分泌偶联的成熟。对葡萄糖代谢和K+和Ca 2+跨膜流动的研究表明，葡萄糖刺激的胰岛素释放减弱是由于未成熟的葡萄糖代谢导致胎儿β细胞质膜中ATP敏感性K+通道的调节受损。在胎儿晚期，葡萄糖也是β细胞复制的强刺激物，葡萄糖的代谢是这一过程的先决条件。葡萄糖通过将β-细胞从静息状态募集到由活跃细胞周期中的细胞组成的增殖区室中来刺激增殖。即使在最大刺激下，增殖区室也占总胰岛细胞群的< 10%。胎儿β细胞的增殖也受到几种肽生长因子的调节，例如生长激素、胰岛素样生长因子I和血小板衍生生长因子。葡萄糖既能诱导刺激-分泌偶联的早熟成熟，又能刺激胎儿β细胞增殖，这一观察结果解释了患有相对轻度高血糖症的糖尿病母亲的后代的宫内高胰岛素血症和β细胞增生。然而，严重的高血糖症，至少在大鼠中诱导时，似乎会延迟而不是刺激β细胞生长。
We review some key aspects of the maturation of stimulus-secretion coupling and the regulation of DNA replication in the fetal beta-cell. During fetal life, the beta-cell shows a poor insulin response to glucose, although it responds to several other nonnutrient stimuli. However, chronic exposure to glucose in excess of basal levels can induce maturation of the stimulus-secretion coupling. Studies of glucose metabolism and the transmembrane flow of K+ and Ca2+ indicate that the attenuated glucose-stimulated insulin release is due to an immature glucose metabolism resulting in impaired regulation of ATP-sensitive K+ channels in the plasma membrane of the fetal beta-cell. In late fetal life, glucose is also a strong stimulus to beta-cell replication, and metabolism of glucose is a prerequisite for this process. Glucose stimulates proliferation by recruiting beta-cells from a resting state into a proliferative compartment composed of cells in an active cell cycle. The proliferative compartment comprises < 10% of the total islet cell population even at maximal stimulation. The proliferation of fetal beta-cells is also regulated by several peptide growth factors such as growth hormone, insulinlike growth factor I, and platelet-derived growth factor. The observation that glucose can both induce precocious maturation of the stimulus-secretion coupling and stimulate proliferation of the fetal beta-cell explains the intrauterine hyperinsulinemia and beta-cell hyperplasia of the offspring of diabetic mothers with relatively mild hyperglycemia. However, severe hyperglycemia, at least when induced in rats, seems to retard rather than stimulate beta-cell growth.