Diabetologia

Increasing a key clock gene in the brain's daily rhythm center may protect eye nerve and blood vessel damage in diabetic mice

Updated

Abstract

Bmal1 overexpression in db/db mice significantly decreased the free-running period and improved retinal neuronal function.

  • Bmal1 overexpression restored retinal neuronal function, as indicated by improvements in electroretinogram responses.
  • Visual acuity and optomotor behaviour were enhanced in mice with Bmal1 overexpression compared to untreated db/db mice.
  • Retinal vascular deficits were significantly reduced following Bmal1 overexpression.
  • Bmal1 overexpression led to decreased fat content in genetically predisposed obese db/db mice.
  • Improved glucose homeostasis was observed in Bmal1-overexpressing mice, along with reduced hepatic gluconeogenesis.
  • Levels of plasma noradrenaline and liver tyrosine hydroxylase were decreased, suggesting altered adrenergic signalling in response to Bmal1 overexpression.

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Funding

Competing interests

Acknowledgements: 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-Bmal1 design. Data availability: All data supporting the findings of this study are included in the paper and the electronic supplementary information. Funding: 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. Authors’ relationships and activities: 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. Contribution statement: 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.
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