Alina Kabaliei, Vitalina Palchyk, Olga Izmailova, Viktoriya Shynkevych, Oksana Shlykova, Igor Kaidashev
{"title":"Long-Term Administration of Omeprazole-Induced Hypergastrinemia and Changed Glucose Homeostasis and Expression of Metabolism-Related Genes","authors":"Alina Kabaliei, Vitalina Palchyk, Olga Izmailova, Viktoriya Shynkevych, Oksana Shlykova, Igor Kaidashev","doi":"10.1155/2024/7747599","DOIUrl":null,"url":null,"abstract":"<i>Introduction</i>. 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. <i>Methods</i>. Healthy adult male BALB/c mice were randomly divided into three equal groups (<span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"-0.0498162 -8.34882 17.789 8.55521\" width=\"17.789pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,0,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,10.158,0)\"></path></g></svg><span></span><svg height=\"8.55521pt\" style=\"vertical-align:-0.2063904pt\" version=\"1.1\" viewbox=\"21.3711838 -8.34882 12.679 8.55521\" width=\"12.679pt\" xmlns=\"http://www.w3.org/2000/svg\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g transform=\"matrix(.013,0,0,-0.013,21.421,0)\"></path></g><g transform=\"matrix(.013,0,0,-0.013,27.661,0)\"></path></g></svg></span> in each one): (1) experimental mice that received OZ 20 mg/kg; (2) control mice that received 30 <i>μ</i>l 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 <i>Sirt1</i>, <i>Pparg</i>, <i>Nfκb1 (p105)</i>, <i>Nfe2l2</i>, <i>Cxcl5</i>, <i>Smad3</i>, <i>H2a.z</i>, and <i>H3f3b</i> were measured by RT-PCR. <i>Result</i>. 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 <i>Sirt1</i>, <i>Pparg</i>, and <i>Cxcl5</i> mRNA expression. There were no differences in <i>β</i>-cell numbers between groups. <i>Conclusion</i>. Long-term OZ treatment induced hypergastrin- and hyperinsulinemia and increased expression of <i>Sirt1</i>, <i>Pparg</i>, and <i>Cxcl5</i> in mouse pancreatic tissues accompanied by specific changes in glucose metabolism. The mechanism of omeprazole-induced <i>Cxcl5</i> mRNA expression and its association with pancreatic cancer risk should be investigated.","PeriodicalId":9007,"journal":{"name":"BioMed Research International","volume":"44 1","pages":""},"PeriodicalIF":2.6000,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BioMed Research International","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1155/2024/7747599","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.