{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:25Z","timestamp":1784557105288,"version":"3.55.0"},"reference-count":54,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,11]]},"abstract":"\n Numerous studies have implicated tumor necrosis factor \u03b1 (TNF\u03b1) in the pathogenesis of type 2 diabetes. However, the role of its primary receptor, TNF receptor 1 (TNFR1), in homeostatic regulation of glucose metabolism is still controversial. In addition to TNF\u03b1, lymphotoxin \u03b1 (LT\u03b1) binds to and activates TNFR1. Thus, TNF\u03b1 and LT\u03b1 together are known as TNF. To delineate the role of TNF signaling in glucose homeostasis, the present study ascertained how TNF signaling deficiency affects major regulatory components of glucose homeostasis. To this end, normal diet-fed male TNFR1-deficient mice (TNFR1\n \u2212\/\u2212<\/jats:sup>\n ), TNF\u03b1\/LT\u03b1\/LT\u03b2 triple-deficient mice (TNF\/LT\n \u22063<\/jats:sup>\n ) and their littermate controls were subjected to intraperitoneal glucose tolerance test, insulin tolerance test and oral glucose tolerance test. The present results showed that TNFR1\n \u2212\/\u2212<\/jats:sup>\n and TNF\/LT\n \u22063<\/jats:sup>\n mice vs their controls had comparable body weight, tolerance to intraperitoneal glucose and sensitivity to insulin. However, their tolerance to oral glucose was significantly increased. Additionally, glucose-induced insulin secretion assessments revealed that TNFR1 or TNF\/LT deficiency significantly increased oral but not intraperitoneal glucose-induced insulin secretion. Consistently, qPCR and immunohistochemistry analyses showed that TNFR1\n \u2212\/\u2212<\/jats:sup>\n and TNF\/LT\n \u22063<\/jats:sup>\n mice vs their controls had significantly increased ileal expression of glucagon-like peptide-1 (GLP-1), one of the primary incretins. Their oral glucose-induced secretion of GLP-1 was also significantly increased. These data collectively suggest that physiological TNF signaling regulates glucose metabolism primarily through effects on GLP-1 expression and secretion and subsequently insulin secretion.\n <\/jats:p>","DOI":"10.1530\/jme-18-0129","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T08:32:09Z","timestamp":1531902729000},"page":"153-161","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":9,"title":["TNF signaling impacts glucagon-like peptide-1 expression and secretion"],"prefix":"10.1530","volume":"61","author":[{"given":"Sufang","family":"Chen","sequence":"first","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"2Department of Geriatric Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"3Department of Bile Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minjie","family":"Chen","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Qin","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianglin","family":"Qiu","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"},{"name":"4Department of Occupational and Environmental Health, School of Public Health, Nantong University, Nantong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"5Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Cao","sequence":"additional","affiliation":[{"name":"6Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhekang","family":"Ying","sequence":"additional","affiliation":[{"name":"1Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref311","doi-asserted-by":"crossref","first-page":"3950","DOI":"10.1210\/en.2015-1361","article-title":"Chronic exposure to TNFalpha impairs secretion of glucagon-like peptide-1","volume":"156","year":"2015","journal-title":"Endocrinology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.cmet.2018.03.001","article-title":"Mechanisms of action and therapeutic application of glucagon-like peptide-1","volume":"27","year":"2018","journal-title":"Cell 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