Bischof M G, Ludwig C, Hofer A, Kletter K, Krebs M, Stingl H, Nowotny P, Waldhäusl W, Roden M
Department of Internal Medicine III, University of Vienna Medical School, Austria.
Horm Metab Res. 2000 Oct;32(10):417-23. doi: 10.1055/s-2007-978664.
Non-obese type 2 diabetic subjects in good metabolic control (n=6, HbA1c 7.0 +/- 0.3%, mean diabetes duration: 5.7 +/- 1 years) and matched non-diabetic subjects (control; n = 6) were studied during hyperinsulinemic (approximately 3 nmol/l)-hypoglycemic (approximately 3.1 mmol/l) clamp tests (0-120 min) and the subsequent recovery period (120-240 min). Plasma glucagon rose gradually but not significantly, whereas norepinephrine and epinephrine similarly increased approximately 2 and approximately 25-fold in both groups. Islet amyloid polypeptide (IAPP) decreased to approximately 41% and approximately 24% of basal values during hypoglycemia and rapidly rose approximately 4.7-fold during the recovery period, while plasma C-peptide remained suppressed in both groups. Within 140 min, plasma free fatty acids similarly decreased to approximately 70 micromol/l (p < 0.05), but then rose to values being approximately 50% higher in diabetic than in control subjects (240 min: 907 +/- 93 vs. 602 +/- 90 micromol/l; p < 0.05). Glucose infusion rates were comparable during hypoglycemia, but approximately 40% lower during recovery in diabetic patients (1.88 +/- 0.27 vs. 3.44 +/- 0.27 mg x kg(-1) x min(-1), p < 0.001). These results demonstrate that (i) hypoglycemia induced by high-dose insulin largely abolishes the counterregulatory response of glucagon, but not of catecholamines in nondiabetic and well-controlled type 2 diabetic subjects, (ii) the rapid posthypoglycemic increase of plasma IAPP occurs independently of plasma insulin, and (iii) the superior rise in plasma free fatty acids may account at least in part for the posthypoglycemic insulin resistance of type 2 diabetic patients.
在高胰岛素血症（约3 nmol/l）-低血糖症（约3.1 mmol/l）钳夹试验（0 - 120分钟）及随后的恢复期（120 - 240分钟）期间，对代谢控制良好的非肥胖2型糖尿病受试者（n = 6，糖化血红蛋白7.0±0.3%，平均糖尿病病程：5.7±1年）和匹配的非糖尿病受试者（对照组；n = 6）进行了研究。血浆胰高血糖素逐渐升高但不显著，而去甲肾上腺素和肾上腺素在两组中同样分别升高约2倍和约25倍。低血糖期间胰岛淀粉样多肽（IAPP）降至基础值的约41%和约24%，恢复期迅速升高约4.7倍，而两组血浆C肽均持续受到抑制。140分钟内，血浆游离脂肪酸同样降至约70 μmol/l（p < 0.05），但随后糖尿病患者的血浆游离脂肪酸升高至比对照组高约50%的值（240分钟时：907±93 vs. 602±90 μmol/l；p < 0.05）。低血糖期间葡萄糖输注率相当，但糖尿病患者恢复期的葡萄糖输注率约低40%（1.88±0.27 vs. 3.44±0.27 mg·kg⁻¹·min⁻¹，p < 0.001）。这些结果表明：（i）高剂量胰岛素诱导的低血糖在很大程度上消除了非糖尿病和血糖控制良好的2型糖尿病受试者中胰高血糖素的反调节反应，但未消除儿茶酚胺的反调节反应；（ii）低血糖后血浆IAPP的快速升高独立于血浆胰岛素发生；（iii）血浆游离脂肪酸的显著升高可能至少部分解释了2型糖尿病患者低血糖后的胰岛素抵抗。
