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Clock genes not only play a critical role in orchestrating circadian rhythms, but also regulate a variety of bodily functions. While\n                      <jats:italic>Bmal1<\/jats:italic>\n                      , a clock gene, is vital for maintaining optimal circadian rhythms, its therapeutic potential in type 2 diabetes remains unexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this study,\n                      <jats:italic>db<\/jats:italic>\n                      \/\n                      <jats:italic>db<\/jats:italic>\n                      mice, a well-established model of type 2 diabetes exhibiting arrhythmic behaviour and complications, were injected stereotaxically with AAV-\n                      <jats:italic>Bmal1<\/jats:italic>\n                      or a control virus into the suprachiasmatic nucleus to evaluate the protective effects of\n                      <jats:italic>Bmal1<\/jats:italic>\n                      overexpression on neurovascular deficits of type 2 diabetes. Given the complex neurovascular network and the eye\u2019s unique accessibility as a transparent system, ocular complications were selected as a model to examine the neuronal functional, behavioural and vascular benefits of central overexpression of\n                      <jats:italic>Bmal1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Bmal1<\/jats:italic>\n                      overexpression decreased the free-running period, which otherwise is lengthened in\n                      <jats:italic>db<\/jats:italic>\n                      \/\n                      <jats:italic>db<\/jats:italic>\n                      mice. Retinal neuronal function was restored on the electroretinogram, along with optomotor behaviour and visual acuity enhancements. Retinal vascular deficits were also significantly reduced. Notably,\n                      <jats:italic>Bmal1<\/jats:italic>\n                      overexpression decreased fat content in genetically predisposed obese\n                      <jats:italic>db\/db<\/jats:italic>\n                      mice compared with the untreated\n                      <jats:italic>db\/db<\/jats:italic>\n                      group. As the suprachiasmatic nucleus is known to regulate hepatic glucose production via sympathetic mechanisms, glycaemic control and pyruvate tolerance tests were evaluated. Glucose homeostasis was improved in\n                      <jats:italic>Bmal1-<\/jats:italic>\n                      overexpressing mice, accompanied by a significant reduction in hepatic gluconeogenesis. Plasma noradrenaline (norepinephrine) and liver tyrosine hydroxylase levels were reduced, indicating a protective regulation of adrenergic signalling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>\n                      Our study highlights the therapeutic potential of central overexpression of a clock gene,\n                      <jats:italic>Bmal1<\/jats:italic>\n                      , to mitigate metabolic and neurovascular deficits of type 2 diabetes, offering a compelling framework for incorporating circadian rhythms into managing diabetes and its complications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06734-1","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T11:53:55Z","timestamp":1777031635000},"page":"2088-2100","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bmal1 overexpression in suprachiasmatic nucleus protects from retinal neurovascular deficits in a mouse model of diabetes"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4083-5712","authenticated-orcid":false,"given":"Neha","family":"Mahajan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7590-5262","authenticated-orcid":false,"given":"Qianyi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6450-6834","authenticated-orcid":false,"given":"Jodi","family":"Lukkes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-2410","authenticated-orcid":false,"given":"Surabhi D.","family":"Abhyankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0190-0505","authenticated-orcid":false,"given":"Ashay D.","family":"Bhatwadekar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"6734_CR1","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1146\/ANNUREV-PHYSIOL-021909-135919","volume":"72","author":"DK Welsh","year":"2010","unstructured":"Welsh DK, Takahashi JS, Kay SA (2010) Suprachiasmatic nucleus: cell autonomy and network properties. 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Yale J Biol Med 92(2):155\u2013167"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06734-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-026-06734-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-026-06734-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:41:27Z","timestamp":1780584087000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-026-06734-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["6734"],"URL":"https:\/\/doi.org\/10.1007\/s00125-026-06734-1","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"assertion":[{"value":"3 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We wish to thank C. Dong (Indiana University School of Medicine) for helpful discussion on liver studies, K. Orr and L. Udari (Islet and Physiology Core, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine) for their technical help with GTT, ITT and Echo MRI studies, A.S. Porter (Michigan State University) for experimental help with tyrosine hydroxylase staining, and W.C. Smith (University of Florida) for help with the AAV-\n                      Bmal1\n                      design.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"All data supporting the findings of this study are included in the paper and the electronic supplementary information.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This work was supported by funding from National Eye Institute grants R01EY027779, R01EY027779-S1 and R01EY032080 to AB, and an unrestricted grant from Research to Prevent Blindness (RPB) to the Department of Ophthalmology, Indiana University School of Medicine.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"AB is an ad hoc District Support Pharmacist at CVS Health\/Aetna. The views of the authors presented in this study do not necessarily reflect those of CVS Health\/Aetna. The remaining authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"NM conceptualised the study and was involved in software use, validation, formal analysis and investigation; and wrote the original draft and reviewed and edited the manuscript. QL conceptualised the study and was involved in software use, validation, formal analysis and investigation; and reviewed and edited the manuscript. JL was involved in software use, formal analysis and investigation (AAV experiments); and reviewed and edited the manuscript. SA was involved in formal analysis; and reviewed and edited the manuscript. AB conceptualised and supervised the study, provided resources, and was involved in project administration and funding acquisition; and reviewed and edited the manuscript. All authors have given final approval for the version to be published. AB is responsible for the integrity of the work as a whole.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}