Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes

Abstract

Objective:The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM).Design:Clinical intervention study with 1-h intravenous adrenaline infusion.Subjects:Eight male overweight T2DM subjects and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by 133Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging. Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue.Results:ATBF increased similarly in both groups during the adrenaline infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from adipose tissue was delayed in overweight T2DM subjects. Glucose uptake in adipose tissue increased in non-T2DM subjects during adrenaline infusion but was unchanged in overweight T2DM subjects. This results in a delayed excess release of NEFA from the adipose tissue in overweight T2DM subjects after cessation of the adrenaline infusion.Conclusion:Capillaries in the adipose tissue are recruited by adrenaline in non-T2DM subjects; however, this response is impaired in overweight T2DM subjects. NEFA, released in adipose tissue during adrenaline stimulation, is insufficiently re-esterified in situ in overweight T2DM subjects, probably owing to increased ATBF after adrenaline infusion and inability to increase adipose tissue glucose uptake.

Postprandial Oxidative Metabolism of Human Brown Fat Indicates Thermogenesis

“…Our data revealed a link between postprandial plasma adrenaline concentrations and BAT oxygen consumption (r = 0.79, p = 0.01), blood flow (r = 0.83, p = 0.005), and BAT NEFA uptake (r = 0.78, p = 0.002), which signifies the complex interactive mechanism of multiple factors involved in postprandial BAT metabolism. Previously, a role of adrenaline in regulating lipoprotein lipase (Pedersen et al, 1999), adipose tissue capillary recruitment (Tobin et al, 2012), PGC-1a, and UCP1 (Sharara-Chami et al, 2010) has been proposed, and based on our data we speculate that adrenaline may act as a BAT metabolic regulator in postprandial state, although further mechanistic studies are required. (G) Postprandial BAT K i was inversely related to plasma NEFA concentrations.…”

Depot- and diabetes-specific differences in norepinephrine-mediated adipose tissue angiogenesis, vascular tone, collagen deposition and morphology in obesity

“…This differential sensitivity to NE was absent in arterioles from obese diabetic subjects in line with the comparable high NE synthesis in both depots and the relative reduction in sensitivity compared with SAT from the non-diabetic obese subjects. This is consistent with the signi cant increase in microvascular volume observed in non-diabetic compared to the diabetic group following intravenous adrenaline infusion [53]. This could also be explained by the NE desensitization in SAT arterioles of diabetic patients, while the response to the thromboxane analogue U46619 was unaffected in these circumstances, suggesting speci c alteration of noradrenergic mechanism in obesity/diabetes.…”

GIP-induced vasodilation in human adipose tissue involves capillary recruitment

“…The blood flow response to feeding is blocked by propranolol infusion (completely in some adipose tissue depots and partially in others) (6), suggesting that it is dependent upon sympathetic activation. The mechanisms behind the induction of the capillary recruitment in the adipose tissues are yet unknown, but a study from our laboratory showed that infusion of adrenaline increased both ATBF and capillary recruitment (26).…”