{"title":"合成糖皮质激素倍他米松的非阶段性治疗会扰乱小鼠的糖代谢。","authors":"","doi":"10.1016/j.lfs.2024.123080","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e. in-phase (administered when endogenous glucocorticoid levels are high) versus out-of-phase (administered when endogenous glucocorticoid levels are low). We investigated the synthetic glucocorticoid betamethasone – which is extensively used in the clinic - and monitored the development of common metabolic side effects in mice upon prolonged treatment, with a particular focus on glucose metabolism.</div></div><div><h3>Methods</h3><div>Male and female C57BL/6J mice were treated with the synthetic glucocorticoid betamethasone in-phase and out-of-phase, and the development of metabolic side effects was monitored.</div></div><div><h3>Results</h3><div>We observed that, compared with in-phase treatment, out-of-phase treatment with betamethasone results in hyperinsulinemia in both male and female C57BL/6J mice. We additionally found that out-of-phase betamethasone treatment strongly reduced insulin sensitivity as compared to in-phase administration during morning measurements. Our study shows that the adverse effects of betamethasone are dependent on the time of treatment with generally less side effects on glucose metabolism with in-phase treatment.</div></div><div><h3>Conclusions</h3><div>This study highlights differences in glucocorticoid outcome based on the time of measurement, advocating that potential circadian variation should be taken into account when studying glucocorticoid biology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Out-of-phase treatment with the synthetic glucocorticoid betamethasone disturbs glucose metabolism in mice\",\"authors\":\"\",\"doi\":\"10.1016/j.lfs.2024.123080\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e. in-phase (administered when endogenous glucocorticoid levels are high) versus out-of-phase (administered when endogenous glucocorticoid levels are low). We investigated the synthetic glucocorticoid betamethasone – which is extensively used in the clinic - and monitored the development of common metabolic side effects in mice upon prolonged treatment, with a particular focus on glucose metabolism.</div></div><div><h3>Methods</h3><div>Male and female C57BL/6J mice were treated with the synthetic glucocorticoid betamethasone in-phase and out-of-phase, and the development of metabolic side effects was monitored.</div></div><div><h3>Results</h3><div>We observed that, compared with in-phase treatment, out-of-phase treatment with betamethasone results in hyperinsulinemia in both male and female C57BL/6J mice. We additionally found that out-of-phase betamethasone treatment strongly reduced insulin sensitivity as compared to in-phase administration during morning measurements. Our study shows that the adverse effects of betamethasone are dependent on the time of treatment with generally less side effects on glucose metabolism with in-phase treatment.</div></div><div><h3>Conclusions</h3><div>This study highlights differences in glucocorticoid outcome based on the time of measurement, advocating that potential circadian variation should be taken into account when studying glucocorticoid biology.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320524006702\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320524006702","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Out-of-phase treatment with the synthetic glucocorticoid betamethasone disturbs glucose metabolism in mice
Objective
Endogenous glucocorticoid levels display a strong circadian rhythm, which is often not considered when synthetic glucocorticoids are prescribed as anti-inflammatory drugs. In this study we evaluated the effect timing of glucocorticoid administration, i.e. in-phase (administered when endogenous glucocorticoid levels are high) versus out-of-phase (administered when endogenous glucocorticoid levels are low). We investigated the synthetic glucocorticoid betamethasone – which is extensively used in the clinic - and monitored the development of common metabolic side effects in mice upon prolonged treatment, with a particular focus on glucose metabolism.
Methods
Male and female C57BL/6J mice were treated with the synthetic glucocorticoid betamethasone in-phase and out-of-phase, and the development of metabolic side effects was monitored.
Results
We observed that, compared with in-phase treatment, out-of-phase treatment with betamethasone results in hyperinsulinemia in both male and female C57BL/6J mice. We additionally found that out-of-phase betamethasone treatment strongly reduced insulin sensitivity as compared to in-phase administration during morning measurements. Our study shows that the adverse effects of betamethasone are dependent on the time of treatment with generally less side effects on glucose metabolism with in-phase treatment.
Conclusions
This study highlights differences in glucocorticoid outcome based on the time of measurement, advocating that potential circadian variation should be taken into account when studying glucocorticoid biology.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.