Impact of intranasal insulin on muscle sympathetic nerve activity and peripheral vascular conductance in healthy young adults

Abstract

Objective: Systemic insulin increases muscle sympathetic nervous system activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action within the peripheral vasculature, whether increased MSNA with insulin stimulation promotes vasoconstriction and increased BP remains unknown. Herein, using intranasal administration of insulin, we examined for the first time central actions of insulin on MSNA, as well as peripheral hemodynamic effects in healthy humans. We hypothesized intranasal insulin would increase MSNA and promote peripheral vasoconstriction and an increase in BP in healthy young adults. Methods: Twenty healthy young adults were randomized into time control [n=13 (5F/8M), 28±1 yrs] or 160 IU of intranasal insulin administered over 5 minutes [n=7 (0F/7M), 27±3 yrs]. MSNA (peroneal microneurography), BP (finger photoplethysmography), and leg blood flow (LBF, femoral Doppler ultrasound) data are reported from baseline and 15 minutes following insulin administration. Leg vascular conductance (LVC = LBF ÷ mean BP x 100) was calculated. Results: Following intranasal administration, MSNA (26±2 to 31±2 bursts/min, p=0.02; n=4) and mean BP (93±2 to 98±3 mmHg, p=0.02) increased while LVC tended to decrease (106±7 to 99±7 mL/min/100 mmHg, p=0.063). Venous systemic insulin and plasma glucose remained unchanged throughout the protocol (p>0.05). During time control experiments, MSNA (25±2 to 25±1 bursts/min, p=0.72; n=9), mean BP (92±2 to 93±2 mmHg, p=0.50), and LVC (80±8 to 81±9 mL/min/100 mmHg, p=0.58) did not differ from baseline. Conclusions: We provide the first evidence that intranasal insulin administration in healthy young adults acutely increases MSNA to promote peripheral vasoconstriction and an increase in BP. These preliminary results have important implications for our understanding of cardiovascular control mechanisms during hyperinsulinemia and provide the opportunity to extend these findings to disease states (e.g., insulin resistance, diabetes) in future studies. Funding: 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.