{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T04:27:14Z","timestamp":1762057634170,"version":"build-2065373602"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council (NSERC)","doi-asserted-by":"publisher","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Manitoba Health Research Council","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}]},{"name":"Research Manitoba","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}]},{"name":"University of Manitoba Graduate Enhancement of Tri-council Stipends","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}]},{"name":"MHRC Doctoral Studentship","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}]},{"name":"Faculty of Science (University of Manitoba) Undergraduate Student Research Award","award":["RGPIN 05937-2017"],"award-info":[{"award-number":["RGPIN 05937-2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Feeding-regulating neurotrophic factors are expressed in both neurons and glial cells. However, nutritional regulation of anorexigenic glial cell line-derived neurotrophic factor (GDNF) and orexigenic mesencephalic astrocyte-derived neurotrophic factor (MANF) expression in specific cell types remains poorly understood. Hypothalamic glucose sensing plays a critical role in the regulation of food intake. It has been theorized that local glucose concentration modulates microglial activity partially via glucose transporter 5 (GLUT5). We hypothesized that an increased local glucose concentration stimulates GDNF expression while inhibiting MANF expression in the hypothalamus and microglia via GLUT5. The present study investigated the effect of glucose on Gdnf and Manf mRNA expression in the mouse hypothalamus and murine microglial cell line SIM-A9. Intracerebroventricular glucose treatment significantly increased Gdnf mRNA levels in the hypothalamus without altering Manf mRNA levels. Exposure to high glucose caused a significant increase in Gdnf mRNA expression and a time-dependent change in Manf mRNA expression in SIM-A9 cells. GLUT5 inhibitor treatment did not block glucose-induced Gdnf mRNA expression in these cells. These findings suggest that microglia are responsive to changes in the local glucose concentration and increased local glucose availability stimulates the expression of microglial GNDF through a GLUT5-independent mechanism, contributing to glucose-induced feeding suppression.<\/jats:p>","DOI":"10.3390\/ijms23137073","type":"journal-article","created":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T09:00:13Z","timestamp":1656234013000},"page":"7073","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glucose Stimulates Glial Cell Line-Derived Neurotrophic Factor Gene Expression in Microglia through a GLUT5-Independent Mechanism"],"prefix":"10.3390","volume":"23","author":[{"given":"Muhammad S.","family":"Aldhshan","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8316-1333","authenticated-orcid":false,"given":"Gursagar","family":"Jhanji","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole J.","family":"Poritsanos","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0836-3506","authenticated-orcid":false,"given":"Tooru M.","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolic Diseases, Department of Physiology & Pathophysiology, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1126\/science.8493557","article-title":"GDNF: A glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons","volume":"260","author":"Lin","year":"1993","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/0361-9230(94)00224-O","article-title":"Glial cell line-derived neurotrophic factor augments midbrain dopaminergic circuits in vivo","volume":"36","author":"Hudson","year":"1995","journal-title":"Brain Res. 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