Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
Biochem Biophys Res Commun. 2011 Jul 1;410(2):345-50. doi: 10.1016/j.bbrc.2011.06.010. Epub 2011 Jun 7.
Fatty acid-induced damage in pancreatic β-cells is assumed to play an important role in the development of type 2 diabetes. Lactogens (prolactin, placental lactogen and growth hormone) improve β-cell survival via STAT5 activation but the molecular targets are incompletely characterized. The aim of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP2, FATP1 and FATP4 were unchanged. RNAi against FAT/CD36 decreased fatty acid-induced apoptosis. Over-expression of constitutively active STAT5 was able to mimic hGH's suppression of FAT/CD36 expression, whereas dominant negative STAT5 was unable to block the effect of hGH indicating that STAT5 did not bind directly to the FAT/CD36 promoter. The hGH-mediated suppression of FAT/CD36 mRNA was associated with a decrease in palmitate uptake and fatty acid-induced basal hyper-secretion of insulin resulting in improved glucose-stimulated insulin secretion. This study suggests that hGH can protect β-cells against fatty acid-induced damages.
脂肪酸诱导的胰腺β细胞损伤被认为在 2 型糖尿病的发生发展中起重要作用。泌乳激素（催乳素、胎盘催乳素和生长激素）通过 STAT5 激活来改善β细胞的存活，但分子靶点尚未完全阐明。本研究旨在研究人生长激素（hGH）对胰腺β细胞中表达的脂肪酸转运和结合蛋白的 mRNA 的影响，并研究其与脂肪酸暴露后β细胞存活的关系。hGH 降低了 FAT/CD36 的 mRNA 水平，而 GPR40、FASN、FABP2、FATP1 和 FATP4 的 mRNA 水平不变。FAT/CD36 的 RNAi 降低了脂肪酸诱导的细胞凋亡。组成型激活 STAT5 的过表达能够模拟 hGH 对 FAT/CD36 表达的抑制作用，而显性失活 STAT5 不能阻断 hGH 的作用，表明 STAT5 不能直接与 FAT/CD36 启动子结合。hGH 介导的 FAT/CD36 mRNA 抑制与棕榈酸摄取减少以及脂肪酸诱导的基础胰岛素过度分泌有关，导致葡萄糖刺激的胰岛素分泌改善。本研究表明，hGH 可以保护β细胞免受脂肪酸诱导的损伤。
