Hill D J, Hogg J, Petrik J, Arany E, Han V K
Lawson Research Institute, St Joseph's Health Centre, London, Ontario, Canada N6A 4V2.
J Endocrinol. 1999 Feb;160(2):305-17. doi: 10.1677/joe.0.1600305.
To determine the role of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the development of the pancreas, and specifically of the islets of Langerhans, we have examined the cellular distribution and developmental changes in the expression of IGFs and IGFBPs in the pancreas of the fetal and neonatal rat between 19.5 days of gestation and postnatal day 28. This represents a period of substantial growth and restructuring of the beta cell component in islets of this species. IGF-I, IGF-II, and IGFBPs-1 to -6 mRNAs were localized by in situ hybridization, and peptides by immunohistochemistry, in histological sections. IGF-II mRNA was highly expressed in islet cells and some ductal epithelial cells in late fetal and early neonatal life, but was barely detectable by postnatal day 28. IGF-II peptide showed a similar distribution. IGF-I mRNA was barely detected in the fetus or neonate and was localized predominantly in the ductal and acinar tissues after postnatal day 7. IGF-I immunoreactivity was associated with some islet cells in the fetus and neonate, suggesting an endocrine rather than a paracrine source. We performed co-localization studies to assess whether the distribution of IGFs within the pancreas might be due to a sequestration by locally produced IGFBPs. The presence of mRNAs for both IGFBPs-1 and -2 was minimal in the pancreas prior to postnatal day 7, although subsequently IGFBP-1 mRNA was seen in islet cells, while IGFBP-2 mRNA was localized in both islets and acinar tissues. In contrast, both IGFBPs-1 and -2 immunoreactivities were identified in islets from late fetal life, suggesting a circulatory source for these IGFBPs during early pancreatic development. IGFBPs-3 to -5 mRNAs and immunoreactivities were identified within islet cells throughout fetal and neonatal life, with IGFBPs-3 and -5 being mainly associated with the alpha cell-rich islet mantle. The results show a compartmentalization of IGFs within pancreatic tissue, reflecting both paracrine and endocrine sources. The localization and action of IGFs in pancreas likely involves sequestration and distribution by endogenous as well as circulating IGFBPs.
为了确定胰岛素样生长因子（IGFs）及其结合蛋白（IGFBPs）在胰腺尤其是胰岛发育中的作用，我们研究了妊娠19.5天至出生后28天的胎鼠和新生鼠胰腺中IGFs和IGFBPs表达的细胞分布及发育变化。这一时期该物种胰岛中的β细胞成分经历了显著的生长和重构。通过原位杂交在组织切片中定位IGF-I、IGF-II以及IGFBPs-1至-6的mRNA，通过免疫组织化学定位肽。IGF-II mRNA在胎儿晚期和新生儿早期的胰岛细胞及一些导管上皮细胞中高表达，但在出生后第28天几乎检测不到。IGF-II肽显示出类似的分布。IGF-I mRNA在胎儿或新生儿中几乎检测不到，出生后第7天主要定位于导管和腺泡组织。IGF-I免疫反应性与胎儿和新生儿的一些胰岛细胞相关，提示其来源为内分泌而非旁分泌。我们进行了共定位研究，以评估胰腺内IGFs的分布是否可能是由于局部产生的IGFBPs的隔离作用。出生后第7天之前，胰腺中IGFBPs-1和-2的mRNA含量极少，不过随后在胰岛细胞中可见IGFBP-1 mRNA，而IGFBP-2 mRNA定位于胰岛和腺泡组织。相反，从胎儿晚期开始在胰岛中就可鉴定出IGFBPs-1和-2的免疫反应性，提示在胰腺早期发育过程中这些IGFBPs来源于循环系统。在整个胎儿期和新生儿期，胰岛细胞中均可鉴定出IGFBPs-3至-5的mRNA和免疫反应性，其中IGFBPs-3和-5主要与富含α细胞的胰岛被膜相关。结果表明胰腺组织内IGFs存在区室化，反映了旁分泌和内分泌来源。IGFs在胰腺中的定位和作用可能涉及内源性以及循环中的IGFBPs的隔离和分布。
