Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.
Sustained beta-cell dysfunction but normalized islet mass in aged thrombospondin-1 deficient mice.
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DOI：
10.1371/journal.pone.0047451
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Carlsson PO
中科院分区：
文献类型：
--
作者：
Drott CJ;Olerud J;Emanuelsson H;Christoffersson G;Carlsson PO
近年来，胰岛内皮细胞已被证明可以通过旁分泌相互作用支持β细胞质量和功能。最近，我们鉴定了一种胰岛内皮特异性糖蛋白——血小板反应蛋白-1 (TSP-1)，它对年轻小鼠的胰岛血管生成和 β 细胞功能具有重要意义。本研究旨在调查 TSP-1 缺陷对胰岛形态和 β 细胞功能的长期影响。在 TSP-1 缺陷小鼠中，观察到胰岛和 β 细胞质量在 10-12 周龄时有所增加，但与野生型对照相比，在 16 周龄之前已恢复正常。 10-12 周和 16 周龄 TSP-1 缺陷动物的胰岛血管分布正常，而一岁动物缺乏 TSP-1 的胰岛血管丰富。通过葡萄糖耐量试验评估，TSP-1 缺陷动物的 β 细胞功能障碍在 10-12 周龄和 52 周龄之间的程度相似。一岁TSP-1缺陷动物的胰岛体内胰岛素分泌能力仅为野生型动物的~15%。使用移植模型，我们在成人 TSP 缺陷胰岛中重建了 TSP-1。与我们之前报道的 TSP-1 重建后恢复功能的新生儿 TSP-1 缺陷胰岛相反，成年胰岛未能恢复。我们得出的结论是，胰岛中的 TSP-1 缺乏会导致出生后血管和内分泌形态的改变，但与慢性 β 细胞功能障碍有关。如果不在生命早期进行替代，TSP-1 缺乏引起的 β 细胞功能障碍是不可逆转的。
Pancreatic islet endothelial cells have in recent years been shown to support beta-cell mass and function by paracrine interactions. Recently, we identified an islets endothelial-specific glycoprotein, thrombospondin-1 (TSP-1), that showed to be of importance for islet angiogenesis and beta-cell function in young mice. The present study aimed to investigate long-term consequences for islet morphology and beta-cell function of TSP-1 deficiency. Islet and beta-cell mass were observed increased at 10–12 weeks of age in TSP-1 deficient mice, but were normalized before 16 weeks of age when compared to wild-type controls. Islet vascularity was normal in 10–12 and 16-week-old TSP-1 deficient animals, whereas islets of one-year-old animals lacking TSP-1 were hypervascular. Beta-cell dysfunction in TSP-1 deficient animals was present at similar magnitudes between 10–12 and 52 weeks of age, as evaluated by glucose tolerance tests. The insulin secretion capacity in vivo of islets in one-year-old TSP-1 deficient animals was only ∼15% of that in wild-type animals. Using a transplantation model, we reconstituted TSP-1 in adult TSP-deficient islets. In contrast to neonatal TSP-1 deficient islets that we previously reported to regain function after TSP-1 reconstitution, adult islets failed to recover. We conclude that TSP-1 deficiency in islets causes changing vascular and endocrine morphological alterations postnatally, but is coupled to a chronic beta-cell dysfunction. The beta-cell dysfunction induced by TSP-1 deficiency is irreversible if not substituted early in life.
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影响因子：
7.8
作者：
Miralles, F;Battelino, T;Czernichow, P;Scharfmann, R
通讯作者：
Scharfmann, R
影响因子：
5.8
作者：
Carlsson, PO;Palm, F;Mattsson, G
通讯作者：
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作者：
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DOI：
10.1073/pnas.171460498
发表时间：
2001-10-23
影响因子：
11.1
作者：
Rodríguez-Manzaneque, JC;Lane, TF;Iruela-Arispe, ML
通讯作者：
Iruela-Arispe, ML
影响因子：
7.7
作者：
Kayali, Ayse G.;Flores, Luis E.;Hayek, Alberto
通讯作者：
Hayek, Alberto