Effect of Intranasal Insulin on Cognitive Function in Diabetic Patients
DOI:
https://doi.org/10.53469/jcmp.2024.06(12).04Keywords:
Intranasal insulin, Diabetes, Cognitive dysfunctionAbstract
A clear association between diabetes and cognitive impairment has been demonstrated in past studies, increasing the incidence of neurodegenerative diseases and accelerating the onset of Alzheimer's disease (AD) and other types of dementia. Many hypothesized mechanisms of diabetes leading to cognitive impairment exist, and the mechanism of insulin resistance has been demonstrated. Transnasal administration of insulin improves recall of spatial memory in healthy subjects in addition to verbal working memory, visuospatial working memory, delayed memory, and cognitive performance in cognitively impaired patients. No safety concerns have been identified in retrospective studies of intranasal insulin. This review aims to assess the potential of intranasal insulin as a treatment for cognitive impairment related to diabetes.
References
Bogush M, Heldt N A, Persidsky Y. Blood brain barrier injury in diabetes: unrecognized effects on brain and cognition: 4 [J]. Journal of Neuroimmune Pharmacology: The Official Journal of the Society on NeuroImmune Pharmacology, 2017, 12(4): 593–601.
Palta P, Carlson M C, Crum R M, et al. Diabetes and cognitive decline in older adults: the ginkgo evaluation of memory study [J]. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 2017, 73(1): 123–130.
Long C, Han X, Yang Y, et al. Efficacy of intranasal insulin in improving cognition in mild cognitive impairment or dementia: a systematic review and meta-analysis [J]. Frontiers in Aging Neuroscience, 2022, 14: 963933.
Matsuzaki T, Sasaki K, Tanizaki Y, et al. Insulin resistance is associated with the pathology of alzheimer disease: the hisayama study [J]. Neurology, 2010, 75(9): 764–770.
Lochhead J J, Davis T P. Perivascular and perineural pathways involved in brain delivery and distribution of drugs after intranasal administration [J]. Pharmaceutics, 2019, 11(11): 598.
Bava B, Sharma K, Yadav V. Intranasal drug delivery system: a review [J]. Research Journal of Science and Technology, 2024: 51–58.
Claxton A, Baker L D, Hanson A, et al. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage alzheimer's disease dementia [J]. J Alzheimers Dis, 2015, 44(3): 897–906.
Ritze Y, Kern W, Ebner E-M, et al. Metabolic and cognitive outcomes of subchronic once-daily intranasal insulin administration in healthy men [J]. Frontiers in Endocrinology, 2018, 9: 663.
Anderson K L, Frazier H N, Maimaiti S, et al. Impact of single or repeated dose intranasal zinc-free insulin in young and aged f344 rats on cognition, signaling, and brain metabolism [J]. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 2017, 72(2): 189–197.
Mooradian A D. Central nervous system complications of diabetes mellitus--a perspective from the blood-brain barrier [J]. Brain Research. Brain Research Reviews, 1997, 23(3): 210–218.
Mogi M, Horiuchi M. Neurovascular coupling in cognitive impairment associated with diabetes mellitus [J]. Circulation Journal: Official Journal of the Japanese Circulation Society, 2011, 75(5): 1042–1048.
Roy S, Kim D. Retinal capillary basement membrane thickening: role in the pathogenesis of diabetic retinopathy [J]. Progress in Retinal and Eye Research, 2021, 82: 100903.
Ehtewish H, Arredouani A, El-Agnaf O. Diagnostic, prognostic, and mechanistic biomarkers of diabetes mellitus-associated cognitive decline [J]. International journal of molecular Sciences, 2022, 23(11): 6144.
Zhang S, Zhang Y, Wen Z, et al. Cognitive dysfunction in diabetes: abnormal glucose metabolic regulation in the brain [J]. Frontiers in Endocrinology, 2023, 14: 1192602.
Dutta B J, Singh S, Seksaria S, et al. Inside the diabetic brain: insulin resistance and molecular mechanism associated with cognitive impairment and its possible therapeutic strategies [J]. Pharmacological Research, 2022, 182: 106358.
Yang X, Zhang S, Dong Z, et al. Insulin resistance is a risk factor for overall cerebral small vessel disease burden in old nondiabetic healthy adult population [J]. Frontiers in Aging Neuroscience, 2019, 11: 127.
Lecordier S, Manrique-Castano D, El Moghrabi Y, et al. Neurovascular alterations in vascular dementia: emphasis on risk factors [J]. Frontiers in Aging Neuroscience, 2021, 13: 727590.
Aljanabi N M, Mamtani S, Al-Ghuraibawi M M H, et al. Alzheimer's and hyperglycemia: role of the insulin signaling pathway and gsk-3 inhibition in paving a path to dementia [J]. Cureus, 2020, 12(2): e6885.
Moheet A, Mangia S, Seaquist E R. Impact of diabetes on cognitive function and brain structure [J]. Annals of the New York Academy of Sciences, 2015, 1353: 60–71.
Callisaya M L, Beare R, Moran C, et al. Type 2 diabetes mellitus, brain atrophy and cognitive decline in older people: a longitudinal study [J]. Diabetologia, 2019, 62(3): 448–458.
Perantie D C, Lim A, Wu J, et al. Effects of prior hypoglycemia and hyperglycemia on cognition in children with type 1 diabetes mellitus [J]. Pediatric Diabetes, 2008, 9(2): 87–95.
Renner D B, Svitak A L, Gallus N J, et al. Intranasal delivery of insulin via the olfactory nerve pathway [J]. Journal of Pharmacy and Pharmacology, 2012, 64(12): 1709–1714.
Zheng M, Wang P. Role of insulin receptor substance-1 modulating pi3k/akt insulin signaling pathway in alzheimer's disease [J]. 3 Biotech, 2021, 11(4): 179.
Zeng Y, Zhang L, Hu Z. Cerebral insulin, insulin signaling pathway, and brain angiogenesis [J]. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 2016, 37(1): 9–16.
Hallschmid M. Intranasal insulin for alzheimer's disease [J]. CNS Drugs, 2021, 35(1): 21–37.
Van Der Heide L P, Kamal A, Artola A, et al. Insulin modulates hippocampal activity‐dependent synaptic plasticity in a n ‐methyl‐ d ‐aspartate receptor and phosphatidyl‐inositol‐3‐kinase‐dependent manner [J]. Journal of Neurochemistry, 2005, 94(4): 1158–1166.
Gendron W H, Fertan E, Roddick K M, et al. Intranasal insulin treatment ameliorates spatial memory, muscular strength, and frailty deficits in 5xfad mice [J]. Physiology & Behavior, 2024, 281: 114583.
Ruegsegger G N, Manjunatha S, Summer P, et al. Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes [J]. FASEB journal: Official publication of the Federation of American Societies for Experimental Biology, 2019, 33(3): 4458–4472.
Chen Y, Guo Z, Mao Y-F, et al. Intranasal insulin ameliorates cerebral hypometabolism, neuronal loss, and astrogliosis in streptozotocin-induced alzheimer's rat model [J]. Neurotoxicity Research, 2018, 33(4): 716–724.
Rajasekar N, Nath C, Hanif K, et al. Intranasal insulin improves cerebral blood flow, nrf-2 expression and bdnf in stz (icv)-induced memory impaired rats [J]. Life Sciences, 2017, 173: 1–10.
Novak V, Mantzoros C S, Novak P, et al. MemAID: memory advancement with intranasal insulin vs. placebo in type 2 diabetes and control participants: a randomized clinical trial [J]. Journal of Neurology, 2022, 269(9): 4817–4835.
Salameh T S, Bullock K M, Hujoel I A, et al. Central nervous system delivery of intranasal insulin: mechanisms of uptake and effects on cognition [J]. J Alzheimers Dis, 2015, 47(3): 715-728.
Mao Y F, Guo Z, Zheng T, et al. Intranasal insulin alleviates cognitive deficits and amyloid pathology in young adult appswe/ps1de9 mice [J]. Aging Cell, 2016, 15(5): 893–902.
Yang H, Tang L, Qu Z, et al. Hippocampal insulin resistance and the sirtuin 1 signaling pathway in diabetes-induced cognitive dysfunction [J]. Neural Regeneration Research, 2021, 16(12): 2465–2474.
Ramos-Rodriguez J J, Sanchez-Sotano D, Doblas-Marquez A, et al. Intranasal insulin reverts central pathology and cognitive impairment in diabetic mother offspring [J]. Molecular Neurodegeneration, 2017, 12(1): 57.
Zhang H, Hao Y, Manor B, et al. Intranasal insulin enhanced resting-state functional connectivity of hippocampal regions in type 2 diabetes [J]. Diabetes, 2015, 64(3): 1025–1034.
Galindo-Mendez B, Trevino J A, McGlinchey R, et al. Memory advancement by intranasal insulin in type 2 diabetes (memaid) randomized controlled clinical trial: design, methods and rationale [J]. Contemporary Clinical Trials, 2020, 89: 105934.
Weinstein G, Davis-Plourde K L, Conner S, et al. Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and alzheimer's disease: pooled analysis from 5 cohorts [J]. PLOS One, 2019, 14(2): e0212293.
Benedict C, Frey W H, Schiöth H B, et al. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments [J]. Experimental Gerontology, 2011, 46(2–3): 112–115.
Nedelcovych M T, Gadiano A J, Wu Y, et al. Pharmacokinetics of intranasal versus subcutaneous insulin in the mouse [J]. ACS Chemical Neuroscience, 2018, 9(4): 809–816.
Kullmann S, Veit R, Peter A, et al. Dose-dependent effects of intranasal insulin on resting-state brain activity [J]. Journal of Clinical Endocrinology and Metabolism, 2018, 103(1): 253–262.
Gaddam M, Singh A, Jain N, et al. A comprehensive review of intranasal insulin and its effect on the cognitive function of diabetics [J]. Cureus, 2021, 13(8): e17219.
Butt D A, Harvey P J. Benefits and risks of antihypertensive medications in the elderly [J]. Journal of Internal Medicine, 2015, 278(6): 599–626.
Anonymous. Nasal route: a novelistic approach for targeted drug delivery to cns [J/OL]. ResearchGate, 2024 [2024–11–29].
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