Intranasal Insulin Enhanced Resting-State Functional Connectivity of Hippocampal Regions in Type 2 Diabetes
Open accessAbstract
Type 2 diabetes mellitus (T2DM) alters brain function and manifests as brain atrophy. Intranasal insulin has emerged as a promising intervention for treatment of cognitive impairment. We evaluated the acute effects of intranasal insulin on resting-state brain functional connectivity in older adults with T2DM. This proof-of-concept, randomized, double-blind, placebo-controlled study evaluated the effects of a single 40 IU dose of insulin or saline in 14 diabetic and 14 control subjects. Resting-state functional connectivity between the hippocampal region and default mode network (DMN) was quantified using functional MRI (fMRI) at 3Tesla. Following insulin administration, diabetic patients demonstrated increased resting-state connectivity between the hippocampal regions and the medial frontal cortex (MFC) as compared with placebo (cluster size: right, P = 0.03) and other DMN regions. On placebo, the diabetes group had lower connectivity between the hippocampal region and the MFC as compared with control subjects (cluster size: right, P = 0.02), but on insulin, MFC connectivity was similar to control subjects. Resting-state connectivity correlated with cognitive performance. A single dose of intranasal insulin increases resting-state functional connectivity between the hippocampal regions and multiple DMN regions in older adults with T2DM. Intranasal insulin administration may modify functional connectivity among brain regions regulating memory and complex cognitive behaviors.
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IN insulin in patients with type 2 diabetes enhances functional connectivity between prefrontal regions and the hippocampal formation.
“IN insulin was also found in patients with type 2 diabetes to enhance functional connectivity between prefrontal regions and the hippocampal formation.131”
From Intranasal insulin (2021) · cites this paper as [131]
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- Authors
- Zhang, H., Hao, Y., Manor, B., Novak, P., Milberg, W., Zhang, J., Fang, J., & Novak, V.
- Affiliations
- Peking University (CN)
- Beth Israel Deaconess Medical Center (US)
- Department of Neurology, University of Massachusetts Medical School, Worcester, MA
- Harvard University (US)
- Corresponding author
- Novak, Vera
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2014-09-22
- Volume
- 64
- Issue
- 3
- Pages
- 1025-1034
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- PMC
- PMC4338591
- OpenAlex
- W2133374742
- Cited by
- 176
- References
- 51
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 17 · 2023: 11 · 2022: 22 · 2021: 16 · 2020: 16 · 2019: 16 · 2018: 11 · 2017: 16 · 2016: 12 · 2015: 9 · 2014: 1
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (5R21-DK-084463-02)
- National Institute on Aging (1R01-AG-0287601-A2)
- National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health (1KL2RR025757-04, 8KL2TR000168-05, 8UL1TR000170-05)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- intranasal insulin, type 2 diabetes, resting-state functional connectivity, hippocampus, default mode network, medial frontal cortex, cognitive impairment, older adults, brain atrophy, memory
- MeSH terms
- Administration, Intranasal, Aged, Brain, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Hippocampus, Humans, Hypoglycemic Agents, Insulin, Magnetic Resonance Imaging, Male, Middle Aged
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