Data from: Sympathetic nervous system activity and anti-lipolytic response to IV-glucose load in subcutaneous adipose tissue of obese and obese type 2 diabetic subjects

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.

本研究旨在探究确诊2型糖尿病（type 2 diabetes, T2D）的肥胖受试者在肾上腺素能刺激后，内源性胰岛素释放对皮下脂肪组织脂解（lipolysis）作用的影响。本研究纳入14名肥胖女性2型糖尿病患者及14名肥胖非2型糖尿病对照受试者，采用微透析技术（microdialysis technique），检测受试者在给予α1,2,β-激动剂（α1,2,β-agonist）去甲肾上腺素（norepinephrine）、α1-激动剂（α1-agonist）去甲苯福林（norfenefrine）及β2-激动剂（β2-agonist）特布他林（terbutaline，浓度均为10^-4 M）后的甘油浓度响应。刺激60分钟后，经静脉给予葡萄糖负荷（intravenous glucose load，剂量为0.5 g/kg瘦体重（lean body mass））。采用乙醇技术（ethanol technique）监测局部血流量。

去甲肾上腺素与去甲苯福林可使甘油透析液浓度分别升高4倍与3倍（两组均p<0.001），脂肪组织的响应模式相似。在激动剂刺激联合葡萄糖输注后，内源性胰岛素释放可抑制去甲肾上腺素存在下的脂解作用，该抑制效应在健康肥胖对照受试者中较2型糖尿病患者更为快速且显著（肥胖对照受试者与2型糖尿病患者相比，p=0.024）。在去甲苯福林存在的情况下，胰岛素诱导的脂解抑制效应在所有研究受试者中无显著差异。特布他林存在时，脂解速率升高2倍，直至内源性胰岛素发挥抑制作用（p<0.001）。分别在去甲苯福林组与特布他林组中，均观察到类似的胰岛素诱导的脂解水平下降。静脉葡萄糖负荷后，脂肪组织血流量未发生明显变化。去甲肾上腺素与去甲苯福林均可轻度降低血流量，但胰岛素可逆转该效应（整个观测时段内p<0.001）。单独使用特布他林以及特布他林联合内源性胰岛素水平升高时，均可增加局部血流量（整个观测时段内p<0.001）。

综上，在调节交感神经系统（sympathetic nervous system）活性后，肥胖2型糖尿病患者与肥胖健康对照受试者之间的胰岛素诱导脂解抑制作用存在差异，该差异推测与去甲肾上腺素介导的β1-肾上腺素能受体（β1-adrenoceptor）刺激有关。