Exenatide prevents statin-related LDL receptor increase and improves insulin secretion in pancreatic beta cells (1.1E7) in a protein kinase A-dependent manner.

IF 2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Lukasz Buldak, Grzegorz Machnik, Estera Skudrzyk, Aleksandra Boldys, Mateusz Maliglowka, Michal Kosowski, Marcin Basiak, Rafal Jakub Buldak, Boguslaw Okopien
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引用次数: 2

Abstract

Statins are primary drugs in the treatment of hyperlipidemias. This group of drugs is known for its beneficial pleiotropic effects (e.g., reduction of inflammatory state). However, a growing body of evidence suggests its diabetogenic properties. The culpable mechanism is not completely understood and might be related to the damage to pancreatic beta cells. Therefore, we conceived an in vitro study to explore the impact of atorvastatin on pancreatic islet beta cells line (1.1.E7). We evaluated the influence on viability, insulin, low-density lipoprotein (LDL) receptor, and proprotein convertase subtilisin/kexin type 9 (PCSK9) expression. A significant drop in mRNA for proinsulin and insulin expression was noted. Concurrently, a rise in LDL receptor at the protein level in cells exposed to atorvastatin was noted. Further experiments have shown that exenatide - belonging to glucagon-like peptide 1 (GLP-1) analogs that are used in a treatment of diabetes and known for its weight reducing properties - can alleviate the observed alterations. In this case, the mechanism of action of exenatide was dependent on a protein kinase A pathway. In conclusion, our results support the hypothesis that statin may have diabetogenic properties, which according to our study is related to reduced insulin expression. The concomitant use of GLP-1 receptor agonist seemed to successfully revert insulin expression.

艾塞那肽以蛋白激酶a依赖的方式阻止他汀类药物相关LDL受体增加并改善胰腺β细胞的胰岛素分泌(1.1E7)。
他汀类药物是治疗高脂血症的主要药物。这组药物以其有益的多效作用(例如,减少炎症状态)而闻名。然而,越来越多的证据表明它具有致糖尿病的特性。致病机制尚不完全清楚,可能与胰腺细胞受损有关。因此,我们设想了一项体外研究,探讨阿托伐他汀对胰岛β细胞系(1.1.E7)的影响。我们评估了对活力、胰岛素、低密度脂蛋白(LDL)受体和枯草杆菌蛋白转化酶/ keexin 9型(PCSK9)表达的影响。胰岛素原和胰岛素mRNA表达显著下降。同时,观察到暴露于阿托伐他汀的细胞中LDL受体蛋白水平升高。进一步的实验表明,艾塞那肽——属于胰高血糖素样肽1 (GLP-1)类似物,用于治疗糖尿病,以其减肥特性而闻名——可以减轻观察到的变化。在这种情况下,艾塞那肽的作用机制依赖于蛋白激酶a途径。总之,我们的研究结果支持他汀类药物可能具有致糖尿病特性的假设,根据我们的研究,这与胰岛素表达降低有关。同时使用GLP-1受体激动剂似乎成功地恢复胰岛素表达。
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来源期刊
Journal of applied biomedicine
Journal of applied biomedicine PHARMACOLOGY & PHARMACY-
CiteScore
2.40
自引率
7.70%
发文量
13
审稿时长
>12 weeks
期刊介绍: Journal of Applied Biomedicine promotes translation of basic biomedical research into clinical investigation, conversion of clinical evidence into practice in all medical fields, and publication of new ideas for conquering human health problems across disciplines. Providing a unique perspective, this international journal publishes peer-reviewed original papers and reviews offering a sensible transfer of basic research to applied clinical medicine. Journal of Applied Biomedicine covers the latest developments in various fields of biomedicine with special attention to cardiology and cardiovascular diseases, genetics, immunology, environmental health, toxicology, neurology and oncology as well as multidisciplinary studies. The views of experts on current advances in nanotechnology and molecular/cell biology will be also considered for publication as long as they have a direct clinical impact on human health. The journal does not accept basic science research or research without significant clinical implications. Manuscripts with innovative ideas and approaches that bridge different fields and show clear perspectives for clinical applications are considered with top priority.
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