Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy.
Islets. 2011 Sep-Oct;3(5):250-8. doi: 10.4161/isl.3.5.16900. Epub 2011 Sep 1.
The search for factors either promoting islets proliferation or survival during adult life is a major issue for both type 1 and 2 diabetes mellitus. Among factors with mitogenic activity on pancreatic β-cells, human placental lactogen (hPL) showed stronger activity when compared to the other lactogen hormones: growth hormone (GH) and prolactin (PRL). The aim of the present work is to elucidate the biological and molecular events of hPL isoform A (hPL-A) activity on human cultured islets. We used pure human pancreatic islets and insulinoma cell lines (βTC-1 and RIN, murine and rat respectively) stimulated with hPL-A recombinant protein and we compared hPL-A activity with that of hGH. We showed that hPL-A inhibits apoptosis, both in insulinoma and human islets, by the phosphorylation of AKT protein. Indeed, the antiapoptotic role of hPL-A was mediated by PI3K, p38 and it was independent by PKA, Erk1/2. Compared with hGH, hPL-A modulated at different intervals and/or intensity by the phosphorylation of JAKs/STATs and MAPKinases. Moreover, hPL-A induced PDX-1 intracellular expression, improving beta cell activity and ameliorating insulin secretion in response to high glucose stimulation. Our data support the idea that hPL-A is involved in the regulation of beta cells activity. Importantly, we found that hPL-A can preserve and improve the ability of purified human pancreatic islets cultured to secrete insulin in vitro.
寻找在成年期促进胰岛增殖或存活的因素是 1 型和 2 型糖尿病的主要问题。在具有促胰腺 β 细胞有丝分裂活性的因素中，人胎盘催乳素（hPL）的活性比其他催乳激素（生长激素（GH）和催乳素（PRL））更强。本工作的目的是阐明 hPL 同工型 A（hPL-A）对人培养胰岛的生物学和分子事件。我们使用纯人胰腺胰岛和胰岛素瘤细胞系（βTC-1 和 RIN，分别为鼠和大鼠）用 hPL-A 重组蛋白刺激，并比较了 hPL-A 与 hGH 的活性。我们表明 hPL-A 通过 AKT 蛋白的磷酸化抑制胰岛素瘤和人胰岛的细胞凋亡。事实上，hPL-A 的抗凋亡作用是由 PI3K、p38 介导的，与 PKA、Erk1/2 无关。与 hGH 相比，hPL-A 通过 JAKs/STATs 和 MAPKinases 的磷酸化以不同的间隔和/或强度进行调节。此外，hPL-A 诱导 PDX-1 细胞内表达，改善β细胞活性，并改善高葡萄糖刺激下的胰岛素分泌。我们的数据支持 hPL-A 参与调节β细胞活性的观点。重要的是，我们发现 hPL-A 可以保持和提高体外培养的纯化人胰腺胰岛分泌胰岛素的能力。
