Abstract
The study aim was to investigate the effect of endogenous insulin release on lipolysis in subcutaneous adipose tissue after adrenergic stimulation in obese subjects diagnosed with type 2 diabetes (T2D). In 14 obese female T2D subjects, or 14 obese non-T2D controls, glycerol concentration was measured in response to the α1,2,ß-agonist norepinephrine, the α1-agonist norfenefrine and the ß2-agonist terbutaline (each 10−4 M), using the microdialysis technique. After 60 minutes of stimulation, an intravenous glucose load (0.5 g/kg lean body mass) was given. Local blood flow was monitored by means of the ethanol technique. Norepinephrine and norfenefrine induced a four and three fold rise in glycerol dialysate concentration (p<0.001, each), with a similar pattern in adipose tissue. Following agonist stimulation and glucose infusion, endogenous insulin release inhibited lipolysis in the presence of norepinephrine, which was more rapid and pronounced in healthy obese controls than in T2D subjects (p = 0.024 obese vs T2D subjects). Insulin-induced inhibition of lipolysis in the presence of norfenefrine was similar in all study participants. In the presence of terbutaline the lipolysis rate increased two fold until the effect of endogenous insulin (p<0.001). A similar insulin-induced decrease in lipolysis was observed for each of the norfenefrine groups and the terbutaline groups, respectively. Adipose tissue blood flow remained unchanged after the iv-glucose load. Both norepinephrine and norfenefrine diminished blood flow slightly, but insulin reversed this response (p<0.001 over the entire time). Terbutaline alone and terbutaline plus increased endogenous insulin augmented local blood flow (p<0.001 over the entire time). In conclusion, a difference in insulin-induced inhibition of lipolysis was observed in obese T2D subjects compared to obese healthy controls following modulation of sympathetic nervous system activity and is assumed to be due to ß1-adrenoceptor mediated stimulation by norepinephrine.
Highlights
Impaired adipose tissue metabolism in obesity plays a key role in obesity-related pathophysiology with diverse metabolic consequences, including hyperglycemia and insulin resistance [1,2]
The glucose concentration was higher in obese type 2 diabetic subjects under basal conditions (F = 7.1, p = 0.013) (Fig 2A), in both groups glucose concentrations rose rapidly to about 14 mM/L and declined towards the baseline during the following 120 minutes
The reduction in glucose concentration was delayed in obese diabetic subjects compared to the controls (F = 6.6, p
Summary
Impaired adipose tissue metabolism in obesity plays a key role in obesity-related pathophysiology with diverse metabolic consequences, including hyperglycemia and insulin resistance [1,2]. Insulin promotes the uptake and intracellular metabolism of glucose in adipose tissue and inhibits lipolysis. The sympathetic nervous system (SNS) innervates white adipose tissue and its activation is necessary for lipolysis [5]. SNS activity has been reported to be either decreased, normal, or increased in obesity [6]. Evidence has been accumulating that low sympathetic nervous system activity and reactivity and/or reduced sensitivity to sympathetic stimulation may play a role in the development and maintenance of obesity [7]. Catecholamines, acting through ß-activation, inhibit insulin action in fat cells and thereby promote insulin resistance [15]. Insulin can acutely reduce cell surface ß-adrenoceptor numbers in these cells, with a subsequent decrease in the lipolytic sensitivity to beta-adrenergic agonists [16]
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