Hamaguchi T, Fukushima H, Uehara M, Wada S, Shirotani T, Kishikawa H, Ichinose K, Yamaguchi K, Shichiri M
Department of Metabolic Medicine, Kumamoto University Medical School, Japan.
Diabetologia. 1991 Nov;34(11):801-6. doi: 10.1007/BF00408354.
An excessive glucagon secretion to intravenous arginine infusion was found in obese hyperinsulinaemic patients with glucose intolerance. This study was designed to determine whether the glucagon hyperresponsiveness to arginine in these patients would improve by insulin infused at a high enough dose to overcome insulin resistance. By infusing high dose insulin during arginine infusion, the previously exaggerated glucagon response to arginine could be normalized. To normalize the abnormal glucagon response, insulin doses of 4.2 +/- 0.7 and 3.8 +/- 0.5 IU were required during arginine infusion in obese hyperinsulinaemic patients with impaired glucose tolerance and Type 2 (non-insulin-dependent) diabetes mellitus, respectively. This achieved plasma peak insulin levels 3 to 4 times higher than those observed in non-obese healthy subjects. Furthermore, we clarified whether or not the effect of normalizing insulin action and/or glycaemic excursions contributed to normalizing the exaggerated glucagon response to arginine in these patients. Blood glucose was clamped while high dose insulin was infused at the same levels as observed during the arginine infusion test with no insulin infusion. As a result, normalization of the exaggerated plasma glucagon response was achieved, whether hyperglycaemia existed or not. These results clearly demonstrate that, similar to non-obese hypoinsulinaemic Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients, the exaggerated Alpha-cell response to arginine infusion in obese hyperinsulinaemic patients with glucose intolerance is secondary to the reduction of insulin action on the pancreatic Alpha cell, and that the expression of insulin action plays an important part in normalizing these abnormalities.
在糖耐量异常的肥胖高胰岛素血症患者中，发现静脉输注精氨酸后胰高血糖素分泌过多。本研究旨在确定，通过输注足够高剂量的胰岛素以克服胰岛素抵抗，这些患者对精氨酸的胰高血糖素高反应性是否会得到改善。在输注精氨酸期间输注高剂量胰岛素，可以使先前对精氨酸夸大的胰高血糖素反应恢复正常。对于糖耐量受损的肥胖高胰岛素血症患者和2型（非胰岛素依赖型）糖尿病患者，在输注精氨酸期间，分别需要4.2±0.7和3.8±0.5 IU的胰岛素剂量，才能使异常的胰高血糖素反应恢复正常。这使得血浆胰岛素峰值水平比非肥胖健康受试者中观察到的水平高出3至4倍。此外，我们还阐明了胰岛素作用和/或血糖波动正常化的作用，是否有助于使这些患者对精氨酸夸大的胰高血糖素反应正常化。在以与无胰岛素输注的精氨酸输注试验期间观察到的相同水平输注高剂量胰岛素时，对血糖进行钳定。结果，无论是否存在高血糖症，血浆中夸大的胰高血糖素反应均恢复正常。这些结果清楚地表明，与非肥胖低胰岛素血症的1型（胰岛素依赖型）和2型（非胰岛素依赖型）糖尿病患者类似，糖耐量异常的肥胖高胰岛素血症患者对精氨酸输注夸大的α细胞反应，继发于胰岛素对胰腺α细胞作用的降低，并且胰岛素作用的表达在使这些异常正常化方面起着重要作用。
