Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells
Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat β-cells
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DOI：
10.1152/ajpendo.00457.2006
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发表时间：
2007-04-01
影响因子：
5.1
通讯作者：
Hiriart, Marcia
中科院分区：
文献类型：
--
作者：
Navarro-Tableros, Victor;Fiordelisio, Tatiana;Hiriart, Marcia
大鼠胰岛β细胞胰岛素分泌、钙通道和GLUT2表达的生理发育[J] .中国生物医学工程学报，2009,31(2):559 - 559。首次发表于2006年12月5日；doi: 10.1152 / ajpendo.00457.2006。-当细胞外葡萄糖浓度升高时，成熟β细胞的胰岛素分泌会急剧增加。葡萄糖刺激的胰岛素分泌依赖于通过电压门控Ca2+通道的Ca2+内流。在胎儿发育期间，这种结构反应并没有很好地建立起来，直到出生后，β细胞才获得葡萄糖敏感性和强劲的分泌。我们比较了从新生大鼠和成年大鼠获得的β细胞中葡萄糖诱导的胰岛素分泌偶联的一些元素，发现新生细胞与成年细胞相比在功能上是不成熟的。我们观察到新生儿细胞分泌较少的胰岛素，不能感知细胞外葡萄糖浓度的变化。这可以部分解释，因为在新生儿Ca2+电流密度和mRNA α 1亚单位Ca2+通道的合成低于成人细胞。有趣的是，新生儿细胞中α 1B、α 1C和α 1D亚基的免疫染色在细胞质和质膜中是相似的，而在成人细胞中主要发生在质膜中。我们还观察到，成人β细胞中GLUT2的表达主要位于细胞膜上，而在新生儿细胞中，葡萄糖转运蛋白主要位于细胞质中。这可以部分解释新生儿β细胞对细胞外葡萄糖不敏感的原因。了解新生儿β细胞的生理和成熟有助于更好地理解2型糖尿病的生理病理，其中β细胞的改变包括l型Ca2+通道和GLUT2表达的减少，导致胰岛素分泌不足。
Physiological development of insulin secretion, calcium channels, and GLUT2 expression of pancreatic rat beta-cells. Am J Physiol Endocrinol Metab 292: E1018-E1029, 2007. First published December 5, 2006; doi:10.1152/ajpendo.00457.2006. - Insulin secretion in mature beta-cells increases vigorously when extracellular glucose concentration rises. Glucose-stimulated insulin secretion depends on Ca2+ influx through voltage-gated Ca2+ channels. During fetal development, this structured response is not well established, and it is after birth that beta-cells acquire glucose sensitivity and a robust secretion. We compared some elements of glucose-induced insulin secretion coupling in beta-cells obtained from neonatal and adult rats and found that neonatal cells are functionally immature compared with adult cells. We observed that neonatal cells secrete less insulin and cannot sense changes in extracellular glucose concentrations. This could be partially explained because in neonates Ca2+ current density and synthesis of mRNA alpha 1 subunit Ca2+ channel are lower than in adult cells. Interestingly, immunostaining for alpha 1B, alpha 1C, and alpha 1D subunits in neonatal cells is similar in cytoplasm and plasma membrane, whereas it occurs predominantly in the plasma membrane in adult cells. We also observed that GLUT2 expression in adult beta-cells is mostly located in the membrane, whereas in neonatal cells glucose transporters are predominantly in the cytoplasm. This could explain, in part, the insensitivity to extracellular glucose in neonatal beta-cells. Understanding neonatal beta-cell physiology and maturation contributes toward a better comprehension of type 2 diabetes physiopathology, where alterations in beta-cells include diminished L-type Ca2+ channels and GLUT2 expression that results in an insufficient insulin secretion.