Role for insulin sensitivity in the cerebrovascular response to hyperinsulinemia in young adults

Abstract

Objective: Cerebral blood flow is highly regulated and cerebrovascular responsiveness to vasodilatory stimuli is predictive of brain health. In preclinical animal models, insulin elicits cerebrovascular dilation and subsequent increases in cerebral blood flow. Contrary to this, preliminary data from our group in a large cohort of healthy humans indicate surrogate measures of cerebral blood flow remain at baseline levels during hyperinsulinemia – although responses were highly variable. In the peripheral circulation, insulin-stimulated vasodilation is closely associated with markers of insulin sensitivity (e.g., elevated fasting glucose, insulin, HOMA-IR); whether these associations translate to the cerebral circulation remains unclear. With this information in mind, we hypothesized the degree of insulin-mediated increases in cerebral blood flow would correlate with indices of peripheral insulin sensitivity.Methods: Middle cerebral artery blood velocity (MCAv) was measured with transcranial Doppler ultrasound in 17 adults (11M/6F, 28±2 yrs, 24±1 kg/m 2 ) at baseline and following a 60-min hyperinsulinemic (40 mU/m 2 body surface area/min), euglycemic infusion. Correlations between MCAv and indices of peripheral insulin sensitivity [i.e., fasting glucose, insulin, HOMA-IR, glucose infusion rate, weight, body mass index (BMI), age, physical activity] were determined. Results: Intravenous insulin infusion increased plasma insulin concentrations (6±1 to 49±3 μIU/mL, p<0.001) with blood glucose maintained (73±4 to 82±6 mg/dL, p=0.196). There was no net change in MCAv during hyperinsulinemia (60±4 to 60±4 cm/s, p=0.930). We observed negative associations between the change in MCAv during hyperinsulinemia (Δ=Insulin–Baseline) and both body weight (R=-0.49, p=0.047) and BMI (R=-0.50, p=0.040). No correlations between ΔMCAv and fasting glucose (p=0.435), insulin (p=0.733), HOMA-IR (p=0.960), age (p=0.132), physical activity (p=0.179), or glucose infusion rate (p=0.599) were observed. Conclusions: As previously shown in these participants, hyperinsulinemia in young adults elicits no net change in MCAv. Any increases in MCAv during hyperinsulinemia occur primarily in individuals with lower body weight and lower BMI. Future studies are needed to translate results to disease states (e.g., diabetes). Margaret W. Mangel Faculty Research Catalyst Fund (JP, JKL), NIH HL137769 (JP), NIH HL130339 (JKL) 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.