{"title":"Chronic intermittent hypoxia affects the expression of IRS - 2/p - Akt/GSK - 3 in the liver of SD rats and its impact on glucose metabolism.","authors":"Hong Wang, Tiantian Guo","doi":"10.1007/s11325-025-03344-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies indicate a strong association between OSA and type 2 diabetes. Currently, the insulin signal transduction pathway and its associated effector proteins have emerged as a focal point in type 2 diabetes research. However, the underlying mechanisms in OSA remain elusive. We have established an experimental model of chronic intermittent hypoxia in SD rats and conducted measurements of their fasting blood glucose, fasting plasma insulin levels, as well as the insulin signaling pathway effector proteins IRS-2, P-Akt, and GSK-3.</p><p><strong>Method: </strong>In the experiment, the gas path control system connected to a sealed glass container regulated the delivery of oxygen and nitrogen, ensuring a minimum oxygen concentration of 6%-12% within the cabin. Forty male Sprague-Dawley rats were divided into five groups (n = 8) and exposed to chronic intermittent hypoxia or normal air environment for 2, 4, 6, and 8 weeks, respectively. Upon completion of the experiment, the rats were anesthetized and euthanized. Immediately thereafter, their fasting blood glucose was measured, and their fasting insulin levels were determined using radioimmunoassay. Finally, the insulin resistance index (HOMA-IR) was calculated based on the steady-state model evaluation method. HE staining was employed to observe the morpho- logical changes of liver cells in each group of rats. Immunohistochemistry was utilized to detect the expression of insulin signaling pathway-related effector proteins, namely IRS-2, p-Akt, and GSK-3, in the liver, with their expression levels expressed as average grayscale values.</p><p><strong>Result: </strong>With the extension of intermittent hypoxia exposure duration, compared to the normal control group, the fasting blood glucose, fasting insulin, and insulin resistance index of rats in each experimental group increased (n = 8, P < 0.05). Additionally, the liver cells of rats exhibited damage and morphological changes. The expression of liver pathway proteins IRS-2 and P-Akt decreased (n = 8, P < 0.05), whereas the expression of GSK-3 protein increased (n = 8, P < 0.05).</p><p><strong>Conclusion: </strong>Chronic intermittent hypoxia activates the proteins IRS-2, P-Akt, and GSK-3 in the hepatic insulin signaling pathway, leading to liver cell damage, insulin resistance, and glucose metabolism disorders.</p>","PeriodicalId":21862,"journal":{"name":"Sleep and Breathing","volume":"29 2","pages":"180"},"PeriodicalIF":2.0000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062185/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Sleep and Breathing","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11325-025-03344-w","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Epidemiological studies indicate a strong association between OSA and type 2 diabetes. Currently, the insulin signal transduction pathway and its associated effector proteins have emerged as a focal point in type 2 diabetes research. However, the underlying mechanisms in OSA remain elusive. We have established an experimental model of chronic intermittent hypoxia in SD rats and conducted measurements of their fasting blood glucose, fasting plasma insulin levels, as well as the insulin signaling pathway effector proteins IRS-2, P-Akt, and GSK-3.
Method: In the experiment, the gas path control system connected to a sealed glass container regulated the delivery of oxygen and nitrogen, ensuring a minimum oxygen concentration of 6%-12% within the cabin. Forty male Sprague-Dawley rats were divided into five groups (n = 8) and exposed to chronic intermittent hypoxia or normal air environment for 2, 4, 6, and 8 weeks, respectively. Upon completion of the experiment, the rats were anesthetized and euthanized. Immediately thereafter, their fasting blood glucose was measured, and their fasting insulin levels were determined using radioimmunoassay. Finally, the insulin resistance index (HOMA-IR) was calculated based on the steady-state model evaluation method. HE staining was employed to observe the morpho- logical changes of liver cells in each group of rats. Immunohistochemistry was utilized to detect the expression of insulin signaling pathway-related effector proteins, namely IRS-2, p-Akt, and GSK-3, in the liver, with their expression levels expressed as average grayscale values.
Result: With the extension of intermittent hypoxia exposure duration, compared to the normal control group, the fasting blood glucose, fasting insulin, and insulin resistance index of rats in each experimental group increased (n = 8, P < 0.05). Additionally, the liver cells of rats exhibited damage and morphological changes. The expression of liver pathway proteins IRS-2 and P-Akt decreased (n = 8, P < 0.05), whereas the expression of GSK-3 protein increased (n = 8, P < 0.05).
Conclusion: Chronic intermittent hypoxia activates the proteins IRS-2, P-Akt, and GSK-3 in the hepatic insulin signaling pathway, leading to liver cell damage, insulin resistance, and glucose metabolism disorders.
期刊介绍：
The journal Sleep and Breathing aims to reflect the state of the art in the international science and practice of sleep medicine. The journal is based on the recognition that management of sleep disorders requires a multi-disciplinary approach and diverse perspectives. The initial focus of Sleep and Breathing is on timely and original studies that collect, intervene, or otherwise inform all clinicians and scientists in medicine, dentistry and oral surgery, otolaryngology, and epidemiology on the management of the upper airway during sleep.
Furthermore, Sleep and Breathing endeavors to bring readers cutting edge information about all evolving aspects of common sleep disorders or disruptions, such as insomnia and shift work. The journal includes not only patient studies, but also studies that emphasize the principles of physiology and pathophysiology or illustrate potentially novel approaches to diagnosis and treatment. In addition, the journal features articles that describe patient-oriented and cost-benefit health outcomes research. Thus, with peer review by an international Editorial Board and prompt English-language publication, Sleep and Breathing provides rapid dissemination of clinical and clinically related scientific information. But it also does more: it is dedicated to making the most important developments in sleep disordered breathing easily accessible to clinicians who are treating sleep apnea by presenting well-chosen, well-written, and highly organized information that is useful for patient care.
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