Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells: possible physiological implications.
Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic beta-cells: possible physiological implications.
复制标题
胰腺β细胞中前脂肪细胞因子1/δ样蛋白/胎儿抗原1的表达、生物合成和释放：可能的生理学意义。
作者：
B. Friedrichsen;C. Carlsson;A. Møldrup;B. Michelsen;C. H. Jensen;B. Teisner;J. Nielsen
前脂肪细胞因子-1（Pref-1）/δ样蛋白/胎儿抗原-1（FA 1）是表皮生长因子样家族的成员。在胚胎组织中广泛表达，而在成人中仅限于肾上腺、垂体前叶、内分泌胰腺、睾丸和卵巢。我们以前克隆Pref-1从新生大鼠胰岛刺激生长激素。本研究的目的是阐明β细胞中Pref-1/FA 1的生物合成和释放，并确定Pref-1/FA 1是否介导GH在胰岛素产生细胞中的促有丝分裂作用。首先，我们研究了Pref-1的生物合成和加工的可溶性形式，FA 1，在胰岛和胰岛素瘤细胞转染Pref-1 cDNA。我们通过ELISA测定了FA 1的释放，并通过在胰岛素阳性胰岛细胞中掺入溴脱氧尿苷（BrdU）测定了FA 1在GH刺激的β细胞增殖中的可能作用。我们发现Pref-1在正常胰岛和RINm 5 F胰岛素瘤细胞中合成，并以两种形式释放到培养基中，其中一种对应于FA 1。GH和催乳素（PRL）刺激Pref-1 mRNA的表达和可溶性形式的释放。而2小时暴露于高葡萄糖或3-异丁基-1-甲基黄嘌呤刺激胰岛素的释放，只有一个小的变化，看到在FA 1的释放，这表明FA 1是由不同的途径比胰岛素释放。然而，长期暴露于高葡萄糖（48小时）增加FA 1分泌，表明FA 1是由葡萄糖调节。无论是FA 1还是GH刺激的胰岛的条件培养基都不能增加β细胞的复制，Pref-1的过表达导致RINm 5 F细胞的增殖减弱。GH刺激的胰岛细胞的免疫细胞化学没有观察到高Pref-1表达和BrdU掺入之间的相关性，胰岛素和Pref-1的水平之间呈反比关系。这些结果表明Pref-1/FA 1不介导GH和PRL的促有丝分裂作用。因此，Pref-1在β细胞中的功能仍然未知。
Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ovaries. We have previously cloned Pref-1 from neonatal rat islets stimulated by GH. The aim of the present study was to elucidate the biosynthesis and release of Pref-1/FA1 in beta-cells and to determine if Pref-1/FA1 is mediating the mitogenic effect of GH in insulin-producing cells. First we studied the biosynthesis and processing of Pref-1 to the soluble form, FA1, in pancreatic islets and insulinoma cells transfected with Pref-1 cDNA. We measured the release of FA1 by ELISA and the possible effect of FA1 in GH-stimulated beta-cell proliferation by incorporation of bromodeoxyuridine (BrdU) in insulin-positive islet cells. We found that Pref-1 was synthesized in normal islets and in RINm5F insulinoma cells and released into the medium in two forms, of which one corresponded to FA1. Both the expression of the mRNA for Pref-1 and the release of the soluble form(s) were stimulated by GH and prolactin (PRL). Whereas 2 h exposure to high glucose or 3-isobutyl-1-methylxanthine stimulated insulin release, only a small change was seen in FA1 release, suggesting that the FA1 is released by a different pathway than insulin. However, long-term exposure (48 h) to high glucose increased FA1 secretion, indicating that FA1 is regulated by glucose. Neither FA1 nor conditioned medium from GH-stimulated islets depleted for GH was able to increase beta-cell replication and overexpression of Pref-1 resulted in attenuated proliferation of the RINm5F cells. By immunocytochemistry of GH-stimulated islet cells no correlation between high Pref-1 expression and BrdU incorporation was observed and there was an inverse relationship between the levels of insulin and Pref-1. These results indicate that Pref-1/FA1 is not mediating the mitogenic effect of GH and PRL. Therefore the function of Pref-1 in the beta-cell remains unknown.
影响因子：
4.8
作者：
T. Brelje;D W Scharp;P E Lacy;L. Ogren;F. Talamantes;M. Robertson;H. G. Friesen;R. L. Sorenson
通讯作者：
T. Brelje;D W Scharp;P E Lacy;L. Ogren;F. Talamantes;M. Robertson;H. G. Friesen;R. L. Sorenson
DOI：
10.1073/pnas.94.8.4011
发表时间：
1997-04-15
影响因子：
11.1
作者：
Moore, KA;Pytowski, B;Lemischka, IR
通讯作者：
Lemischka, IR
影响因子：
4.1
作者：
Mei, BS;Zhao, L;Sul, HS
通讯作者：
Sul, HS