ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2019
Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Brain functions and cognition on transient insulin deprivation in type 1 diabetes.JCI insight · 2021Trial
- α-AMA induced liver failure is associated with elevation of HMGB1 lactylation modification in mice.BMC gastroenterology · 2026Article
- Article
- Improvement in Insulin Sensitivity Prevents Decline in Glucose Uptake, Functional Connectivity, and Volume in the Insulin Resistant Human Brain.Research square · 2025Article
- Loss of insulin signaling in microglia impairs cellular uptake of Aβ and neuroinflammatory response exacerbating AD-like neuropathology.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Brain-immune interactions: implication for cognitive impairments in Alzheimer's disease and autoimmune disorders.Journal of leukocyte biology · 2024Review
- Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease.Scientific reports · 2024Article
- Biliverdin Reductase-A integrates insulin signaling with mitochondrial metabolism through phosphorylation of GSK3β.Redox biology · 2024Article
- Intranasal delivery of mitochondria targeted neuroprotective compounds for traumatic brain injury: screening based on pharmacological and physiological properties.Journal of translational medicine · 2024Review
- High-intensity aerobic, but not resistance or combined, exercise training improves both cardiometabolic health and skeletal muscle mitochondrial dynamics.Journal of applied physiology (Bethesda, Md. : 1985) · 2023Article
- Loss of insulin signaling in astrocytes exacerbates Alzheimer-like phenotypes in a 5xFAD mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Hot Spots for the Use of Intranasal Insulin: Cerebral Ischemia, Brain Injury, Diabetes Mellitus, Endocrine Disorders and Postoperative Delirium.International journal of molecular sciences · 2023Review
- Intranasal Administration of KYCCSRK Peptide Rescues Brain Insulin Signaling Activation and Reduces Alzheimer's Disease-like Neuropathology in a Mouse Model for Down Syndrome.Antioxidants (Basel, Switzerland) · 2023Article
- Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain.Frontiers in endocrinology · 2023Review
- Restoring autophagic function: a case for type 2 diabetes mellitus drug repurposing in Parkinson's disease.Frontiers in neuroscience · 2023Review
- Metabolic Regulation of Mitochondrial Protein Biogenesis from a Neuronal Perspective.Biomolecules · 2022Review
- The Role of Mitochondrial Quality Control in Cognitive Dysfunction in Diabetes.Neurochemical research · 2022Review
- Review
- Insulin action in the brain: cell types, circuits, and diseases.Trends in neurosciences · 2022Review
- Toward the Decipherment of Molecular Interactions in the Diabetic Brain.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Despite the strong association between diabetes and dementia, it remains to be fully elucidated how insulin deficiency adversely affects brain functions. We show that insulin deficiency in streptozotocin-induced diabetic mice decreased mitochondrial ATP production and/or citrate synthase and cytochrome oxidase activities in the cerebrum, hypothalamus, and hippocampus. Concomitant decrease in mitochondrial fusion proteins and increased fission proteins in these brain regions likely contributed to altered mitochondrial function. Although insulin deficiency did not cause any detectable increase in reactive oxygen species (ROS) emission, inhibition of monocarboxylate transporters increased ROS emission and further reduced ATP production, indicating the causative roles of elevated ketones and lactate in counteracting oxidative stress and as a fuel source for ATP production during insulin deficiency. Moreover, in healthy mice, intranasal insulin administration increased mitochondrial ATP production, demonstrating a direct regulatory role of insulin on brain mitochondrial function. Proteomics analysis of the cerebrum showed that although insulin deficiency led to oxidative post-translational modification of several proteins that cause tau phosphorylation and neurofibrillary degeneration, insulin administration enhanced neuronal development and neurotransmission pathways. Together these results render support for the critical role of insulin to maintain brain mitochondrial homeostasis and provide mechanistic insight into the potential therapeutic benefits of intranasal insulin.-Ruegsegger, G. N., Manjunatha, S., Summer, P., Gopala, S., Zabeilski, P., Dasari, S., Vanderboom, P. M., Lanza, I. R., Klaus, K. A., Nair, K. S. Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes.
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Registered trials
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