Endurance or sprint interval exercise, & metformin treatment differently modify insulin-induced vasodilation in skeletal muscle arterioles of obese insulin resistant rats

A key contributor to insulin-mediated glucose uptake is insulin-induced vasodilation of skeletal muscle arterioles, which is impared with obesity and Type 2 diabetes (T2D). Abnormalities in the vascular reactivity to insulin can limit perfusion, and delivery of glucose and insulin to muscle tissue. In human patients with T2D, exercise improves insulin sensitivity and glucose uptake T2D. Furthermore, we have previously shown that daily exercise prevents impairments in insulin-induced vasodilation in OLETF rats. However, the efficacy of exercise interventions which utilize different muscle recruitment patterns (i.e. aerobic vs. sprint training) to ameliorate or reverse impairments in microvascular insulin reactivity has not been elucidated. The current ADA standard of care for T2D is treatment with metformin in combination with a diet and exercise program. Therefore, we studied the effects of endurance exercise and interval sprint training with and without metformin on the vasoreactivity to insulin in skeletal muscle arterioles from red and white muscles

Effects of statins on metabolic adaptations to aerobic exercise training : preliminary findings [abstract]

Emerging evidence suggests statins, unlike exercise, may cause deleterious effects on skeletal muscle oxidative capacity and insulin sensitivity. The purpose of this study was to determine if daily statin therapy altered the ability of exercise to lower fasting plasma insulin and glucose and improve cardiorespiratory fitness

Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men

© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. Interval sprint exercise performed on a manually propelled treadmill, where the hands grip the handle bars, engages lower and upper limb skeletal muscle, but little is known regarding the effects of this exercise modality on the upper limb vasculature. We tested the hypotheses that an acute bout of sprint exercise and 6 weeks of training induces brachial artery (BA) and forearm vascular remodeling, favoring a more compliant system. Before and following a single bout of exercise as well as 6 weeks of training three types of vascular properties/methodologies were examined in healthy men: (1) stiffness of the entire upper limb vascular system (pulse wave velocity (PWV); (2) local stiffness of the BA; and (3) properties of the entire forearm vascular bed (determined by a modified lumped parameter Windkessel model). Following sprint exercise, PWV declined (P \u3c 0.01), indices of BA stiffness did not change (P ≥ 0.10), and forearm vascular bed compliance increased and inertance and viscoelasticity decreased (P ≤ 0.03). Following manually propelled treadmill training, PWV remained unchanged (P = 0.31), indices of BA stiffness increased (P ≤ 0.05) and forearm vascular bed viscoelasticity declined (P = 0.02), but resistance, compliance, and inertance remained unchanged (P ≥ 0.10) compared with pretraining values. Sprint exercise induced a more compliant forearm vascular bed, without altering indices of BA stiffness. These effects were transient, as following training the forearm vascular bed was not more compliant and indices of BA stiffness increased. On the basis of these data, we conclude that adaptations to acute and chronic sprint exercise on a manually propelled treadmill are not uniform along the arterial tree in upper limb

Divergent role of nitric oxide in insulin‐stimulated aortic vasorelaxation between low‐ and high‐intrinsic aerobic capacity rats

Low‐intrinsic aerobic capacity is associated with increased risk for cardiovascular and metabolic diseases and is a strong predictor of early mortality. The effects of intrinsic aerobic capacity on the vascular response to insulin are largely unknown. We tested the hypothesis that rats selectively bred for a low capacity to run (LCR) exhibit vascular dysfunction and impaired vascular reactivity to insulin compared to high capacity running (HCR) rats. Mature female LCR (n = 21) and HCR (n = 17) rats were maintained under sedentary conditions, and in vitro thoracic aortic vascular function was assessed. LCR exhibited greater body mass (13%), body fat (35%), and subcutaneous, perigonadal, and retroperitoneal adipose tissue mass, than HCR. During an intraperitoneal glucose tolerance test, glucose area under the curve (AUC) was not different but insulin AUC was 2‐fold greater in LCR than HCR. Acetylcholine and insulin‐stimulated aortic vasorelaxation was significantly greater in LCR (65.2 ± 3.8%, and 32.7 ± 4.1%) than HCR (55.0 ± 3.3%, and 16.7 ± 2.8%). Inhibition of nitric oxide synthase (NOS) with L‐NAME entirely abolished insulin‐mediated vasorelaxation in the aorta of LCR, with no effect in HCR. LCR rats exhibited greater expression of Insulin Receptor protein, lower Endothelin Receptor‐A protein, a down‐regulation of transcripts for markers of immune cell infiltration (CD11C, CD4, and F4/80) and up‐regulation of pro‐atherogenic inflammatory genes (VCAM‐1 and MCP‐1) in the aorta wall. Contrary to our hypothesis, low‐aerobic capacity was associated with enhanced aortic endothelial function and NO‐mediated reactivity to insulin, despite increased adiposity and evidence of whole body insulin resistance.Rats selectively bred for low‐aerobic capacity displayed enhanced aortic endothelial function and nitric oxide‐mediated insulin‐stimulated vasorelaxation, despite increased adiposity and evidence of whole body insulin resistance. The vascular reactivity to insulin in high‐intrinsic aerobic capacity rats was independent of nitric oxide. Our findings demonstrate that endothelial and nitric oxide insulin‐mediated vasomotor function in the rat aorta is not always associated with aerobic capacity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112223/1/phy212459.pd

Epicardial adipose excision slows the progression of porcine coronary atherosclerosis

BACKGROUND: In humans there is a positive association between epicardial adipose tissue (EAT) volume and coronary atherosclerosis (CAD) burden. We tested the hypothesis that EAT contributes locally to CAD in a pig model. METHODS: Ossabaw miniature swine (n = 9) were fed an atherogenic diet for 6 months to produce CAD. A 15 mm length by 3–5 mm width coronary EAT (cEAT) resection was performed over the middle segment of the left anterior descending artery (LAD) 15 mm distal to the left main bifurcation. Pigs recovered for 3 months on atherogenic diet. Intravascular ultrasound (IVUS) was performed in the LAD to quantify atheroma immediately after adipectomy and was repeated after recovery before sacrifice. Coronary wall biopsies were stained immunohistochemically for atherosclerosis markers and cytokines and cEAT was assayed for atherosclerosis-related genes by RT-PCR. Total EAT volume was measured by non-contrast CT before each IVUS. RESULTS: Circumferential plaque length increased (p < 0.05) in the proximal and distal LAD segments from baseline until sacrifice whereas plaque length in the middle LAD segment underneath the adipectomy site did not increase. T-cadherin, scavenger receptor A and adiponectin were reduced in the intramural middle LAD. Relative to control pigs without CAD, 11β-hydroxysteroid dehydrogenase (11βHSD-1), CCL19, CCL21, prostaglandin D(2) synthase, gp91phox [NADPH oxidase], VEGF, VEGFGR1, and angiotensinogen mRNAs were up-regulated in cEAT. EAT volume increased over 3 months. CONCLUSION: In pigs used as their own controls, resection of cEAT decreased the progression of CAD, suggesting that cEAT may exacerbate coronary atherosclerosis

Vascular adaptation to exercise in humans: Role of hemodynamic stimuli

On the 400th anniversary of Harvey’s Lumleian lectures, this review focuses on “hemodynamic” forces associated with the movement of blood through arteries in humans and the functional and structural adaptations that result from repeated episodic exposure to such stimuli. The late 20th century discovery that endothelial cells modify arterial tone via paracrine transduction provoked studies exploring the direct mechanical effects of blood flow and pressure on vascular function and adaptation in vivo. In this review, we address the impact of distinct hemodynamic signals that occur in response to exercise, the interrelationships between these signals, the nature of the adaptive responses that manifest under different physiological conditions, and the implications for human health. Exercise modifies blood flow, luminal shear stress, arterial pressure, and tangential wall stress, all of which can transduce changes in arterial function, diameter, and wall thickness. There are important clinical implications of the adaptation that occurs as a consequence of repeated hemodynamic stimulation associated with exercise training in humans, including impacts on atherosclerotic risk in conduit arteries, the control of blood pressure in resistance vessels, oxygen delivery and diffusion, and microvascular health. Exercise training studies have demonstrated that direct hemodynamic impacts on the health of the artery wall contribute to the well-established decrease in cardiovascular risk attributed to physical activity. © 2017 the American Physiological Society