Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes

IF 2.6 3区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Alina Kabaliei, Vitalina Palchyk, Olga Izmailova, Viktoriya Shynkevych, Oksana Shlykova, Igor Kaidashev
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Abstract

Introduction. PPIs, or proton pump inhibitors, are the most widely prescribed drugs. There is a debate regarding the relationship between long-term PPI use and the risk of type 2 diabetes mellitus (T2DM). A potential connection between T2DM and PPIs could be an elevated gastrin concentration. This study is aimed at investigating the long-term effects of PPI omeprazole (OZ) on glucose homeostasis and pancreatic gene expression profile in mice. Methods. Healthy adult male BALB/c mice were randomly divided into three equal groups ( in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 μl saline per os; (3) intact mice without any interventions. Mice were treated for 30 weeks. Glucose homeostasis was investigated by fasting blood glucose level, oral glucose tolerance test (GTT), insulin tolerance test (ITT), and basal insulin resistance (HOMA-IR). Serum gastrin and insulin concentration were determined by ELISA. Expressions of Sirt1, Pparg, Nfκb1 (p105), Nfe2l2, Cxcl5, Smad3, H2a.z, and H3f3b were measured by RT-PCR. Result. The ROC analysis revealed an increase in fasting blood glucose levels in OZ-treated mice in comparison with control and intact groups during the 30-week experiment. A slight but statistically significant increase in glucose tolerance and insulin sensitivity was observed in OZ-treated mice within 30 weeks of the experiment. The mice treated with OZ exhibited significant increases in serum insulin and gastrin levels, accompanied by a rise in the HOMA-IR level. These animals had a statistically significant increase in Sirt1, Pparg, and Cxcl5 mRNA expression. There were no differences in β-cell numbers between groups. Conclusion. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of Sirt1, Pparg, and Cxcl5 in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced Cxcl5 mRNA expression and its association with pancreatic cancer risk should be investigated.
长期服用奥美拉唑会诱发高胃泌素血症,并改变葡萄糖稳态和代谢相关基因的表达
简介PPI 或质子泵抑制剂是最广泛使用的处方药。关于长期服用 PPI 与 2 型糖尿病(T2DM)风险之间的关系存在争议。T2DM 与 PPIs 之间的潜在联系可能是胃泌素浓度升高。本研究旨在调查 PPI 奥美拉唑(OZ)对小鼠葡萄糖稳态和胰腺基因表达谱的长期影响。研究方法将健康成年雄性 BALB/c 小鼠随机分为三个等量组(每组):(1) 实验组小鼠接受 OZ 20 mg/kg;(2) 对照组小鼠每次口服 30 μl 生理盐水;(3) 无任何干预措施的完整小鼠。小鼠接受了 30 周的治疗。通过空腹血糖水平、口服葡萄糖耐量试验(GTT)、胰岛素耐量试验(ITT)和基础胰岛素抵抗(HOMA-IR)检测葡萄糖稳态。血清胃泌素和胰岛素浓度通过 ELISA 法测定。通过 RT-PCR 检测 Sirt1、Pparg、Nfκb1 (p105)、Nfe2l2、Cxcl5、Smad3、H2a.z 和 H3f3b 的表达。结果ROC 分析表明,在为期 30 周的实验中,与对照组和完整组相比,OZ 治疗小鼠的空腹血糖水平有所升高。在 30 周的实验中,观察到 OZ 治疗小鼠的葡萄糖耐量和胰岛素敏感性略有增加,但在统计学上有显著意义。接受 OZ 治疗的小鼠的血清胰岛素和胃泌素水平显著增加,同时 HOMA-IR 水平也有所上升。据统计,这些动物的 Sirt1、Pparg 和 Cxcl5 mRNA 表达量明显增加。各组间的β细胞数量没有差异。结论长期服用奥美拉唑可诱导高胃泌素血症和高胰岛素血症,并增加小鼠胰腺组织中 Sirt1、Pparg 和 Cxcl5 的表达,同时伴有葡萄糖代谢的特殊变化。奥美拉唑诱导 Cxcl5 mRNA 表达的机制及其与胰腺癌风险的关系有待研究。
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来源期刊
BioMed Research International
BioMed Research International BIOTECHNOLOGY & APPLIED MICROBIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
6.70
自引率
0.00%
发文量
1942
审稿时长
19 weeks
期刊介绍: BioMed Research International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies covering a wide range of subjects in life sciences and medicine. The journal is divided into 55 subject areas.
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