Caporarello Nunzia, Parrino Cristina, Trischitta Vincenzo, Frittitta Lucia
Endocrine Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
IRCCS Casa Sollievo della Sofferenza, Research Unit of Diabetes and Endocrine Diseases, San Giovanni Rotondo, Italy.
PLoS One. 2017 Aug 2;12(8):e0181190. doi: 10.1371/journal.pone.0181190. eCollection 2017.
Glucagon-like peptide-1 (GLP-1) is a potent gluco-incretin hormone, which plays a central role on pancreatic beta cell proliferation, survival and insulin secreting activity and whose analogs are used for treating hyperglycemia in type 2 diabetes mellitus. Notably, abnormal insulin signaling affects all the above-mentioned aspects on pancreatic beta cells. The aim of our study was to investigate whether the protective effects of GLP1-1 on beta cells are affected by altered insulin receptor signaling. To this end, several effects of GLP-1 were studied in INS-1E rat beta cells transfected either with an inhibitor of insulin receptor function (i.e., the Ectonucleotide Pyrophosphatase Phosphodiesterase 1, ENPP1), or with insulin receptor small interfering RNA, as well as in control cells. Crucial experiments were carried out also in a second cell line, namely the βTC-1 mouse beta cells. Our data indicate that in insulin secreting beta cells in which either ENPP1 was up-regulated or insulin receptor was down-regulated, GLP-1 positive effects on several pancreatic beta cell activities, including glucose-induced insulin secretion, cell proliferation and cell survival, were strongly reduced. Further studies are needed to understand whether such a scenario occurs also in humans and, if so, if it plays a role of clinical relevance in diabetic patients with poor responsiveness to GLP-1 related treatments.
胰高血糖素样肽-1（GLP-1）是一种强效的肠促胰岛素激素，它在胰腺β细胞增殖、存活及胰岛素分泌活性方面发挥核心作用，其类似物被用于治疗2型糖尿病中的高血糖症。值得注意的是，异常的胰岛素信号传导会影响胰腺β细胞上述所有方面。我们研究的目的是调查GLP-1对β细胞的保护作用是否会受到胰岛素受体信号传导改变的影响。为此，我们在转染了胰岛素受体功能抑制剂（即胞外核苷酸焦磷酸酶磷酸二酯酶1，ENPP1）或胰岛素受体小干扰RNA的INS-1E大鼠β细胞以及对照细胞中研究了GLP-1的几种作用。关键实验也在第二种细胞系即βTC-1小鼠β细胞中进行。我们的数据表明，在ENPP1上调或胰岛素受体下调的胰岛素分泌β细胞中，GLP-1对几种胰腺β细胞活性（包括葡萄糖诱导的胰岛素分泌、细胞增殖和细胞存活）的积极作用被大幅降低。还需要进一步研究以了解这种情况是否也发生在人类中，如果是，它在对GLP-1相关治疗反应不佳的糖尿病患者中是否具有临床相关性作用。
