Bolinder J, Sjöberg S, Arner P
Department of Medicine, Huddinge Hospital Karolinska Institute, Stockholm, Sweden.
Diabetologia. 1996 Jul;39(7):845-53. doi: 10.1007/s001250050519.
The adrenergic regulation of adipose tissue lipolysis in response to insulin-induced hypoglycaemia (intravenous infusion of soluble insulin 0.10 IU.kg body weight-1.h-1 until the arterial plasma glucose fell below 2.8 mmol/l) was investigated directly in vivo in 11 insulin-dependent diabetic (IDDM) patients and 12 control subjects, using microdialysis of the extracellular space of abdominal subcutaneous adipose tissue. The tissue glycerol level (lipolysis index) and the escape of ethanol from the perfusion medium (blood flow index) were continuously monitored. During insulin infusion the arterial glucose level was reduced in parallel and the hypoglycaemic nadir was almost identical in the two groups (diabetic patients 2.2 +/- 0.1 and control subjects 2.3 +/- 0.1 mmol/l). While the maximum response of plasma epinephrine to hypoglycaemia was 30% lower in diabetic patients than in the control subjects (p < 0.05), the glycerol levels in adipose tissue and in plasma, as well as in serum non-esterified fatty acids, increased twice as much in the former as in the latter group following hypoglycaemia (p < 0.01). Addition of the beta-adrenoceptor blocker propranolol (10(4) mol/l) to the tissue perfusate almost completely prevented the hypoglycaemia-induced increase in the adipose tissue glycerol level in both groups, whereas in situ perfusion with 10(-4) mol/l of the alpha-adrenoceptor blocker phentolamine resulted in an additional increase in the tissue glycerol levels; during alpha-blockade, the glycerol response to hypoglycaemia remained enhanced by threefold in the diabetic patients (p < 0.01). In both groups local adipose tissue blood flow increased transiently in a similar way after hypoglycaemia; the increase being inhibited by in situ beta-adrenoceptor blockade. We conclude that both alpha- and beta-adrenergic mechanisms regulate adipose tissue lipolysis in response to hypoglycaemia. In IDDM, lipolysis is markedly enhanced following hypoglycaemia, despite a reduced catecholamine secretory response, because of increased beta-adrenoceptor action in adipose tissue.
在11名胰岛素依赖型糖尿病（IDDM）患者和12名对照受试者中，采用腹部皮下脂肪组织细胞外空间微透析技术，直接在体内研究了脂肪组织脂解作用对胰岛素诱导的低血糖（静脉输注可溶性胰岛素0.10 IU·kg体重-1·h-1，直至动脉血浆葡萄糖降至2.8 mmol/L以下）的肾上腺素能调节。持续监测组织甘油水平（脂解指数）和乙醇从灌注介质中的逸出情况（血流指数）。在输注胰岛素期间，两组的动脉血糖水平平行降低，低血糖最低点几乎相同（糖尿病患者2.2±0.1，对照受试者2.3±0.1 mmol/L）。虽然糖尿病患者血浆肾上腺素对低血糖的最大反应比对照受试者低30%（p<0.05），但低血糖后，脂肪组织和血浆中的甘油水平以及血清非酯化脂肪酸水平，在糖尿病患者中升高的幅度是对照受试者的两倍（p<0.01）。向组织灌注液中添加β-肾上腺素能受体阻滞剂普萘洛尔（10-4 mol/L）几乎完全阻止了两组低血糖诱导的脂肪组织甘油水平升高，而用10-4 mol/L的α-肾上腺素能受体阻滞剂酚妥拉明进行原位灌注导致组织甘油水平进一步升高；在α-受体阻滞期间，糖尿病患者对低血糖的甘油反应仍增强了三倍（p<0.01）。两组中，低血糖后局部脂肪组织血流均以类似方式短暂增加；这种增加被原位β-肾上腺素能受体阻滞所抑制。我们得出结论，α-和β-肾上腺素能机制均调节脂肪组织对低血糖的脂解作用。在IDDM中，尽管儿茶酚胺分泌反应降低，但由于脂肪组织中β-肾上腺素能受体作用增强，低血糖后脂解作用明显增强。
