{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T16:33:08Z","timestamp":1779899588124,"version":"3.53.1"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>\n                    D-galactose promotes insulin resistance (IR) and neurodegeneration through hyperglycemia, advanced glycation end products (AGEs), oxidative stress, amyloid-\u03b2 accumulation, and disruption of the insulin signalling pathway, leading to neuroinflammation and neuroapoptosis. The purpose of this study was to investigate the insulin signalling pathway and efficacy of ZnO nanoparticles (ZnO NPs) in alleviating brain IR and neurodegeneration via regulating IRS\/PI3K\/AGER\/APP signalling. In this study, bioinformatic analysis of hub genes and PIP network revealed the interconnection between PI3K\/Akt signalling pathway and neuroinflammation pathway leading to neurodegeneration. Further,\n                    <jats:italic>in vivo<\/jats:italic>\n                    analysis on 4-month-old C57BL\/6 mice was randomised into control (NC), 50 mg\/kg of D-galactose (DC), D-galactose + 450 \u03bcg\/Kg of ZnO NPs (Z1), D-galactose + 650 \u03bcg\/Kg of ZnO NPs (Z2), and D-galactose + 20 mg\/kg of metformin (MF). Blood glucose, Amadori products, conjugated dienes, amyloid-\u03b2 deposition, and gene and protein expression of the IRS\/PI3K\/AGER\/APP signalling pathway were analysed. Our findings illustrated that ZnO NPs (Z1) alleviated hyperglycemia, cleared amyloid-\u03b2 accumulation, maintained neural integrity, lessened fat deposition in the liver, and altered the expression of\n                    <jats:italic>irs2<\/jats:italic>\n                    ,\n                    <jats:italic>pi3k<\/jats:italic>\n                    ,\n                    <jats:italic>ager<\/jats:italic>\n                    , and\n                    <jats:italic>app<\/jats:italic>\n                    genes. Thus, ZnO NPs offer a therapeutic strategy for managing IR and neurodegeneration.\n                  <\/jats:p>","DOI":"10.3389\/fendo.2026.1819985","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:29:51Z","timestamp":1778560191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Zinc oxide nanoparticles mitigate insulin resistance in a D-galactose-induced C57BL\/6 mouse model"],"prefix":"10.3389","volume":"17","author":[{"given":"Kanagavalli","family":"Ramasubbu","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology","place":["Vellore, Tamil Nadu, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devi Rajeswari","family":"V.","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, School of Biosciences and Technology, Vellore 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