Intranasal insulin

Hallschmid, Manfred

doi:10.1111/jne.12934

Cited by 50 publications

(32 citation statements)

References 165 publications

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“…The most effective way of insulin delivery to the brain is its intranasal administration, in which insulin enters directly to the brain, bypassing the blood-brain barrier [ 11 , 12 ]. In clinical trials, the intranasal administration of insulin to patients with Alzheimer’s and other neurodegenerative diseases was shown to improve the cognitive functions (see, for example, [ 15 , 16 , 17 , 18 , 19 ]). Meanwhile, in the course of these trials, the first evidence of the development of central insulin resistance appeared.…”

Section: Discussionmentioning

confidence: 99%

“…The neuroprotective effect of intranasally administered insulin is supported by numerous studies on the prevention of neurodegenerative brain damage in experimental animals [ 1 , 13 , 14 ]. The use of intranasally administered insulin for the treatment of patients with Alzheimer’s disease and mild cognitive deficits leads to a significant improvement in their cognitive functions (see, for example, [ 15 , 16 , 17 , 18 , 19 ]). The clinical trials of intranasally administered insulin as a drug for the treatment of Parkinson’s disease are also in progress [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Захарова

Bayunova

Zorina

et al. 2021

IJMS

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Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na+,K+-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na+,K+-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Захарова

Bayunova

Zorina

et al. 2021

IJMS

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“…Some studies have shown that acute and prolonged intranasal insulin administration alleviates AD neuropathology. Significant improvements were found in memory performance and synaptic plasticity, while increases in regional glucose uptake were also observed [38].…”

Section: Insulin and Other Antidiabetics As A Potential Therapy For Alzheimer's Diseasementioning

confidence: 97%

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

Miziak

Błaszczyk²,

Czuczwar

2021

Pharmaceuticals

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Alzheimer’s disease (AD; progressive neurodegenerative disorder) is associated with cognitive and functional impairment with accompanying neuropsychiatric symptoms. The available pharmacological treatment is of a symptomatic nature and, as such, it does not modify the cause of AD. The currently used drugs to enhance cognition include an N-methyl-d-aspartate receptor antagonist (memantine) and cholinesterase inhibitors. The PUBMED, Medical Subject Heading and Clinical Trials databases were used for searching relevant data. Novel treatments are focused on already approved drugs for other conditions and also searching for innovative drugs encompassing investigational compounds. Among the approved drugs, we investigated, are intranasal insulin (and other antidiabetic drugs: liraglitude, pioglitazone and metformin), bexarotene (an anti-cancer drug and a retinoid X receptor agonist) or antidepressant drugs (citalopram, escitalopram, sertraline, mirtazapine). The latter, especially when combined with antipsychotics (for instance quetiapine or risperidone), were shown to reduce neuropsychiatric symptoms in AD patients. The former enhanced cognition. Procognitive effects may be also expected with dietary antioxidative and anti-inflammatory supplements—curcumin, myricetin, and resveratrol. Considering a close relationship between brain ischemia and AD, they may also reduce post-brain ischemia neurodegeneration. An investigational compound, CN-105 (a lipoprotein E agonist), has a very good profile in AD preclinical studies, and its clinical trial for postoperative dementia is starting soon.

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“…It is known that insulin receptors can be found in significant amounts in the olfactory bulb, hypothalamus, and cerebellum and areas involved in memory, including the hippocampus and limbic system. Additionally, central nervous insulin signalling has been demonstrated to participate in various functions such as peripheral energy and glucose homeostasis, food intake, growth, and neuronal plasticity [ 4 , 5 ]. Intranasal insulin administration represents an efficient instrument to understand better the actual contribution insulin makes to these functions and their potential therapeutic targets [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Possible pathophysiologic mechanisms behind this phenomenon include impaired insulin signalling or insulin resistance in the brain [ 5 , 10 ]. In addition, lower insulin levels in the cerebrospinal fluid and a reduced expression of insulin receptors throughout the central nervous system have been found in patients with Alzheimer's Disease [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

A Comprehensive Review of Intranasal Insulin and Its Effect on the Cognitive Function of Diabetics

Gaddam

Singh

Jain

et al. 2021

Cureus

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Diabetes mellitus continues to be a disease that affects a good percentage of our population. The majority affected need insulin on a day-to-day basis. Before the invention of the first manufactured insulin in 1978, dealing with diabetes took a significant toll on patient's lives. As technology and human innovation prevail, significant advancements have taken place in managing this chronic disease. Patients have an option to decide their mode of insulin delivery. Intranasal insulin, one such form, has a rapid mode of action while effectively controlling postprandial hyperglycemia. It has also been proven to reduce hypoglycemia and insulin resistance problems, which seem to be the main adverse effects of using conventional insulin regularly. However, due to the large dosages needed and high incurring costs, Intranasal Insulin is currently being used as adjunctive therapy along with conventional insulin.We conducted a literature search in PubMed indexed journals using the medical terms "Intranasal insulin," "diabetes," and "cognitive impairment" to provide an overview of the mechanism of action of Intranasal Insulin, its distinctive cognitive benefits, and how it can be compared to the standard parenteral insulin therapy. One unique feature of intranasal insulin is its ability to directly affect the central nervous system, bypassing the blood-brain barrier. Not only does this help in reducing the peripheral side effects of insulin, but it has also proven to play a role in improving the cognitive function of diabetics, especially those who have Alzheimer's or mild cognitive impairment, as decreased levels of insulin in the brain has been shown to impact cognitive function negatively. However, it does come with its limitations of poor absorption through the nasal mucosa due to mucociliary clearance and proteolytic enzymes, our body's natural defence mechanisms. This review focuses on the efficacy of intranasal insulin, its potential benefits, limitations, and role in cognitive improvement in people with diabetes with pre-existing cognitive impairment.

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Intranasal insulin

Cited by 50 publications

References 165 publications

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

Some Candidate Drugs for Pharmacotherapy of Alzheimer’s Disease

A Comprehensive Review of Intranasal Insulin and Its Effect on the Cognitive Function of Diabetics

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