Effect of Intranasal Insulin on Neurovascular Coupling in Healthy Young Adults

ABSTRACT Emerging evidence supports an essential role for insulin signaling in neurovascular coupling (NVC) – the link between neuronal activity and cerebral blood flow. In preclinical animal models, impaired insulin signaling is associated with reduced NVC, highlighting the neurogenic role of insulin. However, it remains unclear whether brain insulin stimulation can enhance NVC in humans. PURPOSE: To examine the acute effect of intranasal insulin delivery on NVC. We hypothesized intranasal insulin would augment NVC in healthy young adults. METHODS: Carotid artery blood flow (CBF, Doppler ultrasound) and middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) were measured during five cyclical trials of 30-sec eyes-closed followed by 40-sec of eyes-open while performing a validated visual search paradigm (Where’s Waldo). Trials were conducted before and 60-min after administering 160 IU of intranasal insulin [n=22 (8F/14M), 27±7 yrs, 26±3 kg/m2] or time control [n=12 (5F/7M), 27±4 yrs, 25±3 kg/m2]. NVC was assessed as the relative (%) increase in CBF and MCAv from baseline during the first 30-sec of visual stimulation, as well as area under the curve (AUC). RESULTS: Baseline CBF and MCAv were maintained over time (time control: 726±159 to 718±164 mL/min, p=0.79; 51±7 to 50±13 cm/s, p=0.79) and were unaffected by intranasal insulin (830±175 to 815±180 mL/min, p=0.39; 55±11 to 51±14 cm/s, p=0.09). CBF and MCAv increased in response to the visual search paradigm, and the peak response was unchanged following both time control (11±9 to 9±9%, p=0.62; 18±12 to 10±12%, p=0.18) and insulin (8±8 to 9±9%, p=0.55; 11±11 to 9±8%, p=0.50). Results were consistent when analyzed as AUC from baseline (p-value range 0.26-0.83). CONCLUSION: Contrary to our hypothesis, there was no acute effect of intranasal insulin on NVC, as assessed by the CBF and MCAv response to visual stimulation. These preliminary findings suggest brain insulin stimulation does not influence neurovascular control mechanisms in the healthy state. Future studies should explore the effects of brain insulin stimulation in diseased states characterized by brain insulin resistance, including diabetes.