{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:47Z","timestamp":1787028467757,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science and Technology, Japan","award":["08102003, 15K19425, and 21K16344"],"award-info":[{"award-number":["08102003, 15K19425, and 21K16344"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sleep apnea syndrome (SAS) is a breathing disorder characterized by recurrent episodes of upper-airway collapse, resulting in intermittent hypoxia (IH) during sleep. Experimental studies with animals and cellular models have indicated that IH leads to attenuation of glucose-induced insulin secretion from pancreatic \u03b2 cells and to enhancement of insulin resistance in peripheral tissues and cells, such as the liver (hepatocytes), adipose tissue (adipocytes), and skeletal muscles (myocytes), both of which could lead to obesity. Although obesity is widely recognized as a major factor in SAS, it is controversial whether the development of SAS could contribute directly to obesity, and the effect of IH on the expression of appetite regulatory genes remains elusive. Appetite is regulated appropriately by both the hypothalamus and the gut as a gut\u2013brain axis driven by differential neural and hormonal signals. In this review, we summarized the recent epidemiological findings on the relationship between SAS and feeding behavior and focused on the anorexigenic effects of IH on the gut\u2013brain axis by the IH-induced up-regulation of proopiomelanocortin and cocaine- and amphetamine-regulated transcript in neuronal cells and the IH-induced up-regulation of peptide YY, glucagon-like peptide-1 and neurotensin in enteroendocrine cells and their molecular mechanisms.<\/jats:p>","DOI":"10.3390\/ijms23010364","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Anorexigenic Effects of Intermittent Hypoxia on the Gut\u2014Brain Axis in Sleep Apnea Syndrome"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4165-1200","authenticated-orcid":false,"given":"Ryogo","family":"Shobatake","sequence":"first","affiliation":[{"name":"Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"},{"name":"Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan"},{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyo","family":"Ota","sequence":"additional","affiliation":[{"name":"Department Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nara City Hospital, 1-50-1 Higashikidera-cho, Nara 630-8305, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ueno","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-4687","authenticated-orcid":false,"given":"Kazuma","family":"Sugie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-0199","authenticated-orcid":false,"given":"Shin","family":"Takasawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/sleep\/29.9.1203","article-title":"Complex sleep apnea syndrome: Is it a unique clinical syndrome?","volume":"29","author":"Morgenthaler","year":"2006","journal-title":"Sleep"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1152\/physrev.00043.2008","article-title":"Pathophysiology of sleep apnea","volume":"90","author":"Dempsey","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"238","DOI":"10.4239\/wjd.v4.i6.238","article-title":"Effect of obstructive sleep apnea on type 2 diabetes mellitus: A comprehensive literature review","volume":"15","author":"Nannapaneni","year":"2013","journal-title":"World J. Diabetes"},{"key":"ref_4","first-page":"113","article-title":"Obstructive sleep apnea as a risk factor for type 2 diabetes mellitus","volume":"5","author":"Rajan","year":"2015","journal-title":"Nat. Sci. Sleep"},{"key":"ref_5","first-page":"130","article-title":"Up-regulation of selenoprotein P and HIP\/PAP mRNAs in hepatocytes by intermittent hypoxia via down-regulation of miR-203","volume":"11","author":"Uchiyama","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.lfs.2011.11.011","article-title":"Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38","volume":"90","author":"Ota","year":"2012","journal-title":"Life Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"475","DOI":"10.5664\/jcsm.3690","article-title":"Effect of obstructive sleep apnea hypopnea syndrome on lipid profile: A meta-regression analysis","volume":"15","author":"Nadeem","year":"2014","journal-title":"J. Clin. Sleep Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/S0140-6736(08)61622-0","article-title":"Obstructive sleep apnoea and its cardiovascular consequences","volume":"373","author":"Bradley","year":"2009","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11897-013-0167-3","article-title":"Sleep apnea, heart failure, and pulmonary hypertension","volume":"10","author":"Javaheri","year":"2013","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.smrv.2014.03.008","article-title":"Cognitive complaints in obstructive sleep apnea","volume":"19","author":"Vaessen","year":"2015","journal-title":"Sleep Med. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/j.1440-1843.2012.02255.x","article-title":"Neurocognitive function in obstructive sleep apnoea: A meta-review","volume":"18","author":"Bucks","year":"2013","journal-title":"Respirology"},{"key":"ref_12","first-page":"203","article-title":"Memory and obstructive sleep apnea: A meta-analysis","volume":"36","author":"Wallace","year":"2013","journal-title":"Sleep"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2147\/NDT.S35974","article-title":"Depressive symptoms and childhood sleep apnea syndrome","volume":"8","author":"Carotenuto","year":"2012","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_14","first-page":"1311","article-title":"Obstructive sleep apnea is a common disorder in the population-a review on the epidemiology of sleep apnea","volume":"8","author":"Franklin","year":"2015","journal-title":"J. Thorac. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.atherosclerosis.2011.07.122","article-title":"Inflammation contributes to the atherogenic role of intermittent hypoxia in apolipoprotein-E knock out mice","volume":"219","author":"Arnaud","year":"2011","journal-title":"Atherosclerosis"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ota, H., Fujita, Y., Yamauchi, M., Muro, S., Kimura, H., and Takasawa, S. (2019). Relationship between intermittent hypoxia and Type 2 diabetes in sleep apnea syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194756"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1164\/rccm.201209-1688OC","article-title":"Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4","volume":"188","author":"Drager","year":"2013","journal-title":"Am. J. Respir. Crit. Care. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1586\/17476348.2.1.75","article-title":"Intermittent hypoxia: The culprit of oxidative stress, vascular inflammation and dyslipidemia in obstructive sleep apnea","volume":"2","author":"Lavie","year":"2008","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1164\/rccm.200612-1771OC","article-title":"Chronic intermittent hypoxia induces atherosclerosis","volume":"175","author":"Savransky","year":"2007","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11325-005-0046-6","article-title":"Activation of nuclear factor \u03baB in obstructive sleep apnea: A pathway leading to systemic inflammation","volume":"10","author":"Htoo","year":"2006","journal-title":"Sleep Breath"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1089\/ars.2008.2400","article-title":"Hypoxia activates NF-\u03baB-dependent gene expression through the canonical signaling pathway","volume":"11","author":"Oliver","year":"2009","journal-title":"Antioxid. Redox Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1378\/chest.127.5.1674","article-title":"Oxidative stress in obstructive sleep apnea","volume":"127","author":"Yamauchi","year":"2005","journal-title":"Chest"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/sleep\/26.1.15","article-title":"Sympathetic over activity in the etiology of hypertension of obstructive sleep apnea","volume":"26","author":"Fletcher","year":"2003","journal-title":"Sleep"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1001\/jama.291.16.2013","article-title":"Risk factors for obstructive sleep apnea in adults","volume":"291","author":"Young","year":"2004","journal-title":"JAMA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1164\/rccm.201303-0448OC","article-title":"Defining phenotypic causes of obstructive sleep apnea. Idetifcation of novel therapeutic targets","volume":"188","author":"Eckert","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2147\/NSS.S124657","article-title":"Obstructive sleep apnea: Current perspectives","volume":"10","author":"Osman","year":"2018","journal-title":"Nat. Sci. Sleep"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1513\/pats.200708-139MG","article-title":"Obstructive sleep apnea and metabolic syndrome: Alterations in glucose metabolism and inflammation","volume":"5","author":"Tasali","year":"2008","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1152\/japplphysiol.00587.2005","article-title":"Excess weight and sleep-disordered breathing","volume":"99","author":"Young","year":"2005","journal-title":"J. Appl. Physiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1164\/ajrccm.154.2.8756795","article-title":"Recognition of obstructive sleep apnea","volume":"154","author":"Strohl","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1378\/chest.103.5.1336","article-title":"Adiposity and cardiovascular risk factors in men with obstructive sleep apnea","volume":"103","author":"Levinson","year":"1993","journal-title":"Chest"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1097\/00007611-198909000-00007","article-title":"Sleep apnea: Prevalence of risk factors in a general population","volume":"82","author":"Phillips","year":"1989","journal-title":"South Med. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1001\/archinte.1994.00420150073007","article-title":"Sleep apnea and sleep disruption in obese patients","volume":"154","author":"Vgontzas","year":"1994","journal-title":"Arch. Intern. Med."},{"key":"ref_33","first-page":"19","article-title":"Body mass index and neuropsychological and emotional variables: Joint contribution for the screening of sleep apnoea syndrome in obese","volume":"14","author":"Ribeiro","year":"2021","journal-title":"Sleep Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1001\/jama.284.23.3015","article-title":"Longitudinal study of moderate weight change and sleep-disordered breathing","volume":"284","author":"Peppard","year":"2000","journal-title":"JAMA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/S2213-2600(15)00043-0","article-title":"Prevalence of sleep-disordered breathing in the general population: The HypnoLaus study","volume":"3","author":"Heinzer","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1097\/00005537-200010000-00022","article-title":"Obstructive sleep apnea syndrome: A comparison between Far-East Asian and white men","volume":"110","author":"Li","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1080\/00325481.2021.1914466","article-title":"A community study of the risk for obstructive sleep apnea and respiratory inflammation in an adult Chinese population","volume":"133","author":"Zhang","year":"2021","journal-title":"Postgrad. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.smrv.2016.07.001","article-title":"Obstructive sleep apnea and energy balance regulation: A systematic review","volume":"34","author":"Shechter","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1378\/chest.09-0360","article-title":"Interactions between obesity and obstructive sleep apnea: Implications for treatment","volume":"137","author":"Caples","year":"2010","journal-title":"Chest"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.appet.2014.03.019","article-title":"Liking for high fat foods in patients with obstructive sleep apnoea","volume":"78","author":"Smith","year":"2014","journal-title":"Appetite"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1016\/j.jand.2019.10.016","article-title":"Associations between red meat intake and sleep parameters in patients with obstructive sleep apnea","volume":"120","author":"Kechribari","year":"2020","journal-title":"J. Acad. Nutr. Diet"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kechribari, I., Kontogianni, M.D., Georgoulis, M., Lamprou, K., Vagiakis, E., and Yiannakouris, N. (2021, November 25). Higher refined Cereal Grain intake is Positively Associated with Apnoea-Hypopnoea Index in Patients with Obstructive Sleep Apnoea. Available online: https:\/\/onlinelibrary.wiley.com\/doi\/full\/10.1111\/jhn.12933.","DOI":"10.1111\/jhn.12933"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1017\/jns.2021.24","article-title":"Dietary patterns and sleep disorders in Mexican adults from a National Health and Nutrition Survey","volume":"10","year":"2021","journal-title":"J. Nutr. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.clnesp.2018.09.077","article-title":"Relationship of evening meal with sleep quality in obese individuals with obstructive sleep apnea","volume":"29","author":"Re","year":"2019","journal-title":"Clin. Nutr. ESPE"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00109-015-1274-2","article-title":"Hypoxia-inducible factors and hypertension: Lessons from sleep apnea syndrome","volume":"93","author":"Nanduri","year":"2015","journal-title":"J. Mol. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1113\/jphysiol.2006.114033","article-title":"Heterozygous HIF-1\u03b1 deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia","volume":"577","author":"Peng","year":"2006","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1089\/ars.2007.1691","article-title":"HIF-1-dependent respiratory, cardiovascular, and redox responses to chronic intermittent hypoxia","volume":"9","author":"Semenza","year":"2007","journal-title":"Antioxid. Redox Signal."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.1074\/jbc.M407706200","article-title":"Ca2+\/calmodulin kinase-dependent activation of hypoxia inducible factor 1 transcriptional activity in cells subjected to intermittent hypoxia","volume":"280","author":"Yuan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"16767","DOI":"10.1074\/jbc.M901790200","article-title":"Genome-wide association of hypoxia-inducible factor (HIF)-1\u03b1 and HIF-2\u03b1 DNA binding with expression profiling of hypoxia-inducible transcripts","volume":"284","author":"Mole","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1152\/physiol.00045.2008","article-title":"Regulation of oxygen homeostasis by hypoxia-inducible factor 1","volume":"24","author":"Semenza","year":"2009","journal-title":"Physiology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1152\/physrev.00030.2011","article-title":"Adaptive and maladaptive cardiorespiratory responses to continuous and intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2","volume":"92","author":"Prabhakar","year":"2012","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"15117","DOI":"10.1074\/jbc.271.25.15117","article-title":"The role of the aryl hydrocarbon receptor nuclear translocator (ARNT) in hypoxic induction of gene expression. Studies in ARNT-deficient cells","volume":"271","author":"Wood","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.5664\/jcsm.8682","article-title":"Patients with obstructive sleep apnea present with chronic upregulation of serum HIF-1\u03b1 protein","volume":"16","author":"Gabryelska","year":"2020","journal-title":"J. Clin. Sleep Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4903","DOI":"10.1523\/JNEUROSCI.4768-08.2009","article-title":"NADPH oxidase is required for the sensory plasticity of the carotid body by chronic intermittent hypoxia","volume":"29","author":"Peng","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"10763","DOI":"10.1523\/JNEUROSCI.2307-10.2010","article-title":"NADPH oxidase-dependent regulation of T-type Ca2+ channels and ryanodine receptors mediate the augmented exocytosis of catecholamines from intermittent hypoxia-treated neonatal rat chromaffin cells","volume":"30","author":"Souvannakitti","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1002\/jcp.22640","article-title":"Hypoxia-inducible factor 1 mediates increased expression of NADPH oxidase-2 in response to intermittent hypoxia","volume":"226","author":"Yuan","year":"2011","journal-title":"J. Cell Physiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2217\/epi.15.24","article-title":"Epigenetic regulation by histone demethylases in hypoxia","volume":"7","author":"Hancock","year":"2015","journal-title":"Epigenomics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1152\/physiolgenomics.00045.2021","article-title":"Lysine demethylase KDM6B regulates HIF-1\u03b1-mediated systemic and cellular responses to intermittent hypoxia","volume":"53","author":"Nanduri","year":"2021","journal-title":"Physiol. Genom."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1164\/rccm.200504-637OC","article-title":"Association of sleep apnea and type II diabetes: A population-based study","volume":"172","author":"Reichmuth","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1378\/chest.07-0828","article-title":"Obstructive sleep apnea and type 2 diabetes: Interacting epidemics","volume":"133","author":"Tasali","year":"2008","journal-title":"Chest"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gabryelska, A., Chrzanowski, J., Sochal, M., Kaczmarski, P., Turkiewicz, S., Ditmer, M., Karuga, F.F., Czupryniak, L., and Bia\u0142asiewicz, P. (2021). Nocturnal oxygen saturation parameters as independent risk factors for Type 2 diabetes mellitus among obstructive sleep apnea patients. J. Clin. Med., 10.","DOI":"10.1183\/23120541.sleepandbreathing-2021.66"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1925424","DOI":"10.1155\/2016\/1925424","article-title":"Levels of serum 25(OH)VD3, HIF-1\u03b1, VEGF, vWf, and IGF-1 and their correlation in type 2 diabetes patients with different urine albumin creatinine ratio","volume":"2016","author":"Shao","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Nagao, A., Kobayashi, M., Koyasu, S., Chow, C.C.T., and Harada, H. (2019). HIF-1\u2013dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020238"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.freeradbiomed.2008.11.026","article-title":"\u03b2-cell death and proliferation after intermittent hypoxia: Role of oxidative stress","volume":"46","author":"Xu","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1126\/science.8420005","article-title":"Cyclic ADP-ribose in insulin secretion from pancreatic \u03b2 cells","volume":"259","author":"Takasawa","year":"1993","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"26052","DOI":"10.1016\/S0021-9258(19)74275-6","article-title":"Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP","volume":"268","author":"Takasawa","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1074\/jbc.273.5.2497","article-title":"Cyclic ADP-ribose and inositol 1,4,5-trisphospate as alternate second messengers for intracellular Ca2+ mobilization in normal and diabetic \u03b2-cells","volume":"273","author":"Takasawa","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1074\/jbc.274.4.1869","article-title":"CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion","volume":"274","author":"Kato","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S462","DOI":"10.2337\/diabetes.51.2007.S462","article-title":"Recent advances in the Okamoto model: The CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in \u03b2-cells","volume":"51","author":"Okamoto","year":"2002","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bbrc.2010.05.051","article-title":"A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene","volume":"397","author":"Takasawa","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2183\/pjab.97.022","article-title":"Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracelllular Ca2+ mobilization and Reg ([Regenerating gene] protein)-Reg receptor system for cell regeneration","volume":"79","author":"Okamoto","year":"2021","journal-title":"Proc. Jpn. Acad. Ser. B Phys. Biol. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0021-9258(18)69176-8","article-title":"A novel gene activated in regenerating islets","volume":"263","author":"Terazono","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3589","DOI":"10.1073\/pnas.91.9.3589","article-title":"Pancreatic beta-cell replication and amelioration of surgical diabetes by Reg protein","volume":"91","author":"Watanabe","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1517\/14728222.2016.1123691","article-title":"Regenerating gene (REG) product and its potential clinical usage","volume":"20","author":"Takasawa","year":"2016","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1365-2362.2004.01419.x","article-title":"Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients","volume":"34","author":"Shervani","year":"2004","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.lfs.2013.09.001","article-title":"Pancreatic \u03b2-cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene","volume":"93","author":"Ota","year":"2013","journal-title":"Life Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Takeda, Y., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Ota, H., Kawaguchi, R., and Takasawa, S. (2021). Intermittent hypoxia upregulates the renin and Cd38 mRNAs in renin-producing cells via the downregulation of miR-203. Int. J. Mol. Sci., 22.","DOI":"10.1183\/13993003.congress-2021.PA2393"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Uchiyama, T., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Shobatake, R., Ota, H., Takeda, M., Ohbayashi, C., and Takasawa, S. (2019). Intermittent hypoxia up-regulates CCL2, RETN, and TNF\u03b1 mRNAs in adipocytes via down-regulation of miR-452. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081960"},{"key":"ref_79","unstructured":"Takasawa, S., Shobatake, R., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Uchiyama, T., Tsuchida, C., and Ota, H. (2019, January 2\u20136). Up-regulation of diabetes-associated myokines by intermittent hypoxia in mammalian skeletal muscle cells. Proceedings of the IDF World Diabetes Congress, Busan, Korea."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1887-P","DOI":"10.2337\/db20-1887-P","article-title":"Intermittent hypoxia increased the expressions of interleukin (IL)-8, osteonectin, and myonectin via OCT1 and NRF2 binding to the promoters in muscle cells","volume":"69","author":"Takasawa","year":"2020","journal-title":"Diabetes"},{"key":"ref_81","first-page":"453","article-title":"Up-regulation of IL-8, osteonectin, and myonectin mRNAs by intermittent hypoxia via OCT1- and NRF2-mediated mechanisms in skeletal muscle cells","volume":"63","author":"Takasawa","year":"2020","journal-title":"Diabetologia"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Uchiyama, T., Ota, H., Ohbayashi, C., and Takasawa, S. (2021). Effect of intermittent hypoxia on cytokine expression involved in insulin resistance. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222312898"},{"key":"ref_83","first-page":"217","article-title":"Hypothalamus as an endocrine organ","volume":"5","author":"Clarke","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"T25","DOI":"10.1530\/JOE-13-0398","article-title":"Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance","volume":"220","author":"Schneeberger","year":"2014","journal-title":"J. Endocrinol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1507\/endocrj.K10E-077","article-title":"The role of gut hormones and the hypothalamus in appetite regulation","volume":"57","author":"Suzuki","year":"2010","journal-title":"Endocr. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.cell.2015.02.023","article-title":"Neural control of energy balance: Translating circuits to therapies","volume":"161","author":"Gautron","year":"2015","journal-title":"Cell"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/S0092-8674(03)01081-X","article-title":"Obesity wars: Molecular progress confronts an expanding epidemic","volume":"116","author":"Flier","year":"2004","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/j.neubiorev.2008.05.025","article-title":"Galanin: A potential role in mesolimbic dopamine-mediated instrumental behavior","volume":"32","author":"Robinson","year":"2008","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1111\/j.1471-4159.2006.04090.x","article-title":"Anatomical distribution and biochemical characterization of the novel RFamide peptide 26RFa in the human hypothalamus and spinal cord","volume":"99","author":"Bruzzone","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yfrne.2010.06.001","article-title":"Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction","volume":"32","author":"Lawrence","year":"2011","journal-title":"Front. Neuroendocrinol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.neuron.2017.06.014","article-title":"Toward a wiring diagram understanding of appetite control","volume":"95","author":"Andermann","year":"2017","journal-title":"Neuron"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neuropharm.2016.08.024","article-title":"Role of glutamatergic neurotransmission in the enteric nervous system and brain-gut axis in health and disease","volume":"111","author":"Filpa","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.cell.2016.05.011","article-title":"Sensory neurons that detect stretch and nutrients in the digestive system","volume":"166","author":"Williams","year":"2016","journal-title":"Cell"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cell.2018.08.049","article-title":"A neural circuit for gut-induced reward","volume":"175","author":"Han","year":"2018","journal-title":"Cell"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"eaat5236","DOI":"10.1126\/science.aat5236","article-title":"A gut-brain neural circuit for nutrient sensory transduction","volume":"361","author":"Kaelberer","year":"2018","journal-title":"Science"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/s00018-015-2083-z","article-title":"Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota","volume":"73","author":"Bauer","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"120","DOI":"10.4103\/1817-1737.82440","article-title":"Metabolic syndrome, insulin resistance, fibrinogen, homocysteine, leptin, and C-reactive protein in obese patients with obstructive sleep apnea syndrome","volume":"6","author":"Basoglu","year":"2011","journal-title":"Ann. Thorac. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s00408-008-9082-x","article-title":"Association of sleep apnea severity and obesity with insulin resistance, C-reactive protein, and leptin levels in male patients with obstructive sleep apnea","volume":"186","author":"Kapsimalis","year":"2008","journal-title":"Lung"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"486","DOI":"10.5664\/JCSM.1314","article-title":"Lack of association between impaired glucose tolerance and appetite regulating hormones in patients with obstructive sleep apnea","volume":"7","author":"Papaioannou","year":"2011","journal-title":"J. Clin. Sleep Med."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"895","DOI":"10.5664\/jcsm.4942","article-title":"Among metabolic factors, significance of fasting and postprandial increases in acyl and desacyl ghrelin and the acyl\/desacyl ratio in obstructive sleep apnea before and after treatment","volume":"11","author":"Chihara","year":"2015","journal-title":"J. Clin. Sleep Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4103\/1817-1737.65050","article-title":"Ghrelin, leptin, adiponectin, and resistin levels in sleep apnea syndrome: Role of obesity","volume":"5","author":"Ursavas","year":"2010","journal-title":"Ann. Thorac. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e24368","DOI":"10.1097\/MD.0000000000024368","article-title":"The differences in plasma\/serum ghrelin levels between obstructive sleep apnea-hypopnea patients and controls: A protocol for systematic review and meta-analysis","volume":"100","author":"Sun","year":"2021","journal-title":"Medicine"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1513\/AnnalsATS.201510-697OC","article-title":"Plasma incretin levels and dipeptidyl peptidase-4 activity in patients with obstructive sleep apnea","volume":"13","author":"Matsumoto","year":"2016","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biocel.2017.12.012","article-title":"Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells","volume":"95","author":"Shobatake","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"H751","DOI":"10.1152\/ajpheart.01016.2006","article-title":"Acute intermittent hypoxia activates myocardial cell survival signaling","volume":"292","author":"Park","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Shobatake, R., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Uchiyama, T., Ota, H., Takahashi, N., Ueno, S., and Sugie, K. (2019). Intermittent hypoxia up-regulates gene expressions of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and neurotensin (NTS) in enteroendocrine cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081849"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:55:36Z","timestamp":1760169336000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,29]]},"references-count":106,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010364"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010364","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,29]]}}}