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胰岛素对年轻成年人脑血流指标和脑血管顺应性的影响。

Effect of insulin on indices of cerebral blood flow and cerebrovascular compliance in young adults.

作者信息

Shariffi Brian, Harper Jennifer L, McMillan Neil J, Gonsalves Anna M, Bond Braden J, Pipkins Aubrey M, Shoemaker Leena N, Manrique-Acevedo Camila, Padilla Jaume, Limberg Jacqueline K

机构信息

Department of Nutrition and Exercise Physiology, University of Missouri, Columbia, Missouri, United States.

NextGen Precision Health, University of Missouri, Columbia, Missouri, United States.

出版信息

Am J Physiol Heart Circ Physiol. 2025 Jan 1;328(1):H21-H28. doi: 10.1152/ajpheart.00668.2024. Epub 2024 Nov 25.

Abstract

Insulin has important vasodilatory effects in the peripheral circulation, but less is known about insulin's role in cerebrovascular control. Herein, we hypothesized both systemic (intravenous) and local (intranasal) insulin administration would increase indices of cerebral blood flow and reduce cerebrovascular compliance (Ci) in young adults. Participants were assigned to one of four separate protocols. Middle cerebral artery blood velocity (MCAv, transcranial Doppler ultrasound) and blood pressure (BP, finger photoplethysmography) were measured at baseline and at ) 2 min of carbon dioxide (CO) air breathing (high flow control), ) 60 min of euglycemic intravenous insulin infusion (40 mU/m body surface area/min), ) 60 min following 160 IU of intranasal insulin, ) 60 minutes of time control. Ci was calculated (modified Windkessel model). Intravenous insulin increased serum insulin (6.0 ± 2.6 to 52.7 ± 12.7 μIU/mL, < 0.001), whereas serum insulin was reduced following intranasal insulin (6.9 ± 4.5 to 4.9 ± 1.8 μIU/mL, = 0.030). MCAv increased in response to CO (60 ± 13 to 69 ± 11 cm/s, < 0.001) but was unchanged with time control (50 ± 7 to 49 ± 8, = 0.658) and both insulin conditions (intravenous: 61 ± 13 to 62 ± 17 cm/s, = 0.531; intranasal: 57 ± 12 to 51 ± 15 cm/s; = 0.061). In contrast, Ci remained at baseline levels over time ( = 0.438) and was reduced from baseline under CO and both insulin conditions (CO, < 0.001; intravenous, = 0.021; intranasal, = 0.001). Contrary to our hypothesis, there was no effect of systemic or local insulin administration on resting MCAv in young adults; however, both systemic and local insulin administration reduced Ci. These findings advance our understanding of the cerebrovascular response to acute insulin exposure. Insulin has important vasodilatory effects in the peripheral circulation, but less is known about the role of insulin in cerebrovascular control. Contrary to our hypothesis, there was no effect of systemic (intravenous) nor local (intranasal) insulin administration on middle cerebral artery blood velocity; however, both systemic and local insulin administration reduced cerebrovascular compliance. Our findings advance our understanding of the cerebrovascular response to insulin and may have implications in the context of known metabolic disturbances.

摘要

胰岛素在外周循环中具有重要的血管舒张作用,但胰岛素在脑血管调控中的作用却鲜为人知。在此,我们假设全身(静脉注射)和局部(鼻内)给予胰岛素均可增加年轻成年人的脑血流量指标并降低脑血管顺应性(Ci)。参与者被分配到四个不同方案中的一个。在基线时以及在以下情况下测量大脑中动脉血流速度(MCAv,经颅多普勒超声)和血压(BP,手指光电容积描记法):)二氧化碳(CO₂)空气呼吸2分钟(高流量对照);)正常血糖静脉输注胰岛素60分钟(40 mU/m²体表面积/分钟);)鼻内给予160 IU胰岛素后60分钟;)60分钟的时间对照。计算Ci(改良Windkessel模型)。静脉注射胰岛素可使血清胰岛素升高(从6.0±2.6 μIU/mL升至52.7±12.7 μIU/mL,P<0.001),而鼻内给予胰岛素后血清胰岛素降低(从6.9±4.5 μIU/mL降至4.9±1.8 μIU/mL,P = 0.030)。MCAv对CO₂有反应而升高(从60±13 cm/s升至69±11 cm/s,P<0.001),但在时间对照时无变化(从50±7 cm/s降至49±8 cm/s,P = 0.658),在两种胰岛素给药情况下也无变化(静脉注射:从61±13 cm/s升至62±17 cm/s,P = 0.531;鼻内:从57±12 cm/s降至51±15 cm/s;P = 0.061)。相反,Ci随时间保持在基线水平(P = 0.438),在CO₂和两种胰岛素给药情况下均从基线降低(CO₂,P<0.001;静脉注射,P = 0.021;鼻内,P = 0.001)。与我们的假设相反,全身或局部给予胰岛素对年轻成年人静息状态下的MCAv没有影响;然而,全身和局部给予胰岛素均降低了Ci。这些发现增进了我们对脑血管对急性胰岛素暴露反应的理解。胰岛素在外周循环中具有重要的血管舒张作用,但胰岛素在脑血管调控中的作用却鲜为人知。与我们的假设相反,全身(静脉注射)和局部(鼻内)给予胰岛素对大脑中动脉血流速度均无影响;然而,全身和局部给予胰岛素均降低了脑血管顺应性。我们的发现增进了我们对脑血管对胰岛素反应的理解,并且可能在已知代谢紊乱的背景下具有意义。

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