Impact of Intranasal Insulin on Cerebral Blood Flow and Cerebrovascular Reactivity in Healthy Young Adults

Objective: Adults with obesity and insulin resistance exhibit impaired cerebrovascular reactivity and endothelial dysfunction, which increases the risk of dementia and Alzheimer’s disease. Impairments in cerebrovascular health have been attributed to vascular insulin resistance and emerging data support the use of intranasal insulin as a potential therapeutic intervention. Although mechanisms are unclear, the benefits of intranasal insulin may in part be mediated by changes in cerebral blood flow and/or cerebrovascular reactivity. Using intranasal administration of insulin, we examined the acute effect of central insulin on resting cerebral blood flow as well as reactivity to inhaled carbon dioxide. We hypothesized intranasal insulin would increase indices of 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, 25±3 kg/m2] or 160 IU of intranasal insulin administered over 5 min [n=7 (0F/7M), 27±3 yrs, 25±3 kg/m2]. 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 MCAv and CBF from baseline during 3 min of carbon dioxide air breathing (+7.5±0.5 mmHg). 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 administration. 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 indices of cerebral blood flow and/or cerebrovascular reactivity in healthy young adults. Future studies should examine the cerebrovascular effects of intranasal administration in disease states ( e.g., obesity, insulin resistance, Alzheimer’s disease). CAFNR Joy of Discovery (JKL, JP) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.