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Microglial production of nitric oxide (NO) requires the consumption of NADPH. NADPH consumed in this process is regenerated from NADP\n                      <jats:sup>+<\/jats:sup>\n                      primarily through the hexose monophosphate shunt, which can utilize only glucose as a substrate. These factors predict that glucose availability can be rate\u2010limiting for glial NO production. To test this prediction, cultured astrocytes and microglia were incubated with lipopolysaccharide and interferon\u2010\u03b3 to promote expression of inducible nitric oxide synthase, and the rate of NO production was assessed at defined glucose concentrations. Increased NO production was detected only in cultures containing microglia. The NO production was markedly slowed at glucose concentrations below 0.5\u00a0mM, and comparably reduced by inhibition of the hexose monophosphate shunt with 6\u2010aminonicotinamide. Reduced NO production caused by glucose deprivation was partly reversed by malate, which fuels NADPH production by malate dehydrogenase, and by NADPH itself. These findings highlight the role of the hexose monophosphate shunt in fueling NO synthesis and suggest that microglial NO production in the brain may be limited at sites of low glucose availability, such as abscesses or other compartmentalized infections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15522-fig-0006-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jnc.15522","type":"journal-article","created":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T19:15:01Z","timestamp":1632942901000},"page":"1008-1015","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Glucose availability limits microglial nitric oxide production"],"prefix":"10.1111","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2492-901X","authenticated-orcid":false,"given":"Erika","family":"Castillo","sequence":"first","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"},{"name":"Neurology Service San Francisco Veterans Affairs Health Care System San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3955-3046","authenticated-orcid":false,"given":"Ebony","family":"Mocanu","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"},{"name":"Neurology Service San Francisco Veterans Affairs Health Care System San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8706-9443","authenticated-orcid":false,"given":"G\u04e7khan","family":"Uruk","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"},{"name":"Neurology Service San Francisco Veterans Affairs Health Care System San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3664-5359","authenticated-orcid":false,"given":"Raymond A.","family":"Swanson","sequence":"additional","affiliation":[{"name":"Department of Neurology University of California San Francisco San Francisco California USA"},{"name":"Neurology Service San Francisco Veterans Affairs Health Care System San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0162-3109(85)90025-6"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2070"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.08.008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13486"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2334"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-010-8105-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2007.04.026"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.4049\/jimmunol.149.8.2736","article-title":"Activated microglia mediate neuronal cell injury via a nitric oxide mechanism","volume":"149","author":"Chao C. 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