Insulin-induced changes in skeletal muscle microvascular perfusion are dependent upon perivascular adipose tissue in women

Abstract

Aims/hypothesisObesity increases the risk of cardiovascular disease and type 2 diabetes, partly through reduced insulin-induced microvascular vasodilation, which causes impairment of glucose delivery and uptake. We studied whether perivascular adipose tissue (PVAT) controls insulin-induced vasodilation in human muscle, and whether altered properties of PVAT relate to reduced insulin-induced vasodilation in obesity.MethodsInsulin-induced microvascular recruitment was measured using contrast enhanced ultrasound (CEU), before and during a hyperinsulinaemic–euglycaemic clamp in 15 lean and 18 obese healthy women (18–55 years). Surgical skeletal muscle biopsies were taken on a separate day to study perivascular adipocyte size in histological slices, as well as to study ex vivo insulin-induced vasoreactivity in microvessels in the absence and presence of PVAT in the pressure myograph. Statistical mediation of the relation between BMI and microvascular recruitment by PVAT was studied in a mediation model.ResultsObese women showed impaired insulin-induced microvascular recruitment and lower metabolic insulin sensitivity compared with lean women. Microvascular recruitment was a mediator in the association between obesity and insulin sensitivity. Perivascular adipocyte size, determined in skeletal muscle biopsies, was larger in obese than in lean women, and statistically explained the difference in microvascular recruitment between obese and lean women. PVAT from lean women enhanced insulin-induced vasodilation in isolated skeletal muscle resistance arteries, while PVAT from obese women revealed insulin-induced vasoconstriction.Conclusions/interpretationPVAT from lean women enhances insulin-induced vasodilation and microvascular recruitment whereas PVAT from obese women does not. PVAT adipocyte size partly explains the difference in insulin-induced microvascular recruitment between lean and obese women.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-015-3606-8) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Iloprost infusion prevents the insulin‐induced reduction in skeletal muscle microvascular blood volume but does not enhance peripheral glucose uptake in type 2 diabetic patients

“…Gain (0), focal depth (2‐4 cm), ultrasound frequency (2 MHz) and dynamic range (50 dB) were standardized across all measurements. Acoustic intensities (AIs) were analysed using the Image Processing toolbox in MATLAB, version R2012a (Mathworks, Natick, Massachusetts) as described previously . The derived AIs were log‐compressed and therefore linearized to arbitrary units (AU) on pixel level before the data were fitted to the exponential function.…”

Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue

“…1 to clarify this point. Mesenteric PVAT is a common PVAT depot that is studied for its relevance to alterations in vascular response and blood pressure (5,23,43,49,71,72), whereas PVAT around skeletal muscle arteries is more associated with mechanisms of insulin resistance (7,27,47,48,74). Therefore, mesenteric PVAT was the most relevant PVAT for us to study.…”

Comparisons between perivascular adipose tissue and the endothelium in their modulation of vascular tone

“…Normal adipose tissue tends to be in a non‐inflammatory state, while obesity results in abnormal adipokine production, oxidative stress, hypoxia and inflammation of the adipose tissue (Achike et al, ). PVAT dysfunction is also associated with an up‐regulation of vasoconstricting factors (Almabrouk et al, ) and has been implicated in obesity (Greenstein et al, ; Meijer et al, ) and hypertension (Aghamohammadzadeh et al, ). PVAT dysfunction has been shown to contribute to the obesity‐related endothelial dysfunction (Ketonen et al, ) and smooth muscle cell dysfunction (Greenstein et al, ).…”