Article Title



Brian Shariffi, Neil McMillan, Dain Jacob, Jennifer Harper, Camila Manrique-Acevedo, Jaume Padilla and Jacqueline Limberg

University of Missouri, Columbia, MO

Objective: Adults with obesity and insulin resistance exhibit impaired cerebrovascular reactivity, which increases the risk of Alzheimer’s disease. Impairments in cerebrovascular health have been attributed to vascular insulin resistance and emerging data support intranasal insulin as a potential therapeutic intervention. Although mechanisms are unclear, the benefits of intranasal insulin may be mediated by changes in cerebral blood flow and/or cerebrovascular reactivity. Therefore, we examined the acute effect of intranasal insulin on resting cerebral blood flow as well as reactivity to inhaled carbon dioxide. We hypothesized intranasal insulin would increase cerebral blood flow and cerebrovascular reactivity in healthy young adults.

Methods: Nineteen healthy young adults were randomized into time control [n=12 (5F/7M), 27±1 yrs] or 160 IU of intranasal insulin administered over 5 min [n=7 (0F/7M), 27±3 yrs]. Carotid artery blood flow (CBF, Doppler ultrasound) and middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) were measured prior to and 60 min following insulin administration and/or time control. In a subset of participants (time control, n=10; insulin, n=5), cerebrovascular reactivity was assessed as the relative (%) increase in CBF and MCAv from baseline during 3 min of carbon dioxide air breathing.

Results: Blood glucose and plasma insulin remained unchanged throughout the protocol (both, p>0.05). CBF (712±39 to 727±40 mL/min, p=0.45) and MCAv (50±3 to 52±3 cm/s, p=0.50) remained at baseline levels following the 60-min time control condition. Similarly, resting CBF (901±60 to 908±58 mL/min, p=0.78) and MCAv (54±5 to 52±5 cm/s, p=0.41) did not differ from baseline following intranasal insulin. Carbon dioxide breathing led to an elevation in CBF and MCAv, and their respective increases were unaffected by time control (33±5 to 37±7%, p=0.58; 49±6 to 58±9%, p=0.32) or intranasal insulin (25±3 to 24±5%, p=0.93; 39±6 to 46±6%, p=0.49).

Conclusions: Contrary to our hypothesis, acute intranasal insulin administration had no effect on cerebral blood flow or cerebrovascular reactivity in healthy young adults. Future studies should examine the cerebrovascular effects of intranasal insulin in disease states (e.g., obesity, insulin resistance, Alzheimer’s disease).

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