ABNORMAL GLUCAGON-RESPONSE TO ARGININE AND ITS NORMALIZATION IN OBESE HYPERINSULINEMIC PATIENTS WITH GLUCOSE-INTOLERANCE - IMPORTANCE OF INSULIN ACTION ON PANCREATIC ALPHA-CELLS
ABNORMAL GLUCAGON-RESPONSE TO ARGININE AND ITS NORMALIZATION IN OBESE HYPERINSULINEMIC PATIENTS WITH GLUCOSE-INTOLERANCE - IMPORTANCE OF INSULIN ACTION ON PANCREATIC ALPHA-CELLS
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DOI：
10.1007/bf00408354
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发表时间：
1991-11-01
期刊：
影响因子：
8.2
通讯作者：
SHICHIRI, M
中科院分区：
文献类型：
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作者：
HAMAGUCHI, T;FUKUSHIMA, H;SHICHIRI, M
在伴有葡萄糖耐受不良的肥胖高胰岛素血症患者中，发现静脉注射精氨酸会导致胰高血糖素分泌过多。本研究旨在确定这些患者中胰高血糖素对精氨酸的高反应性是否会通过以足够高的剂量输注胰岛素以克服胰岛素抵抗而改善。通过在精氨酸输注期间输注高剂量胰岛素，可以使先前对精氨酸的过度胰高血糖素反应正常化。为了使异常胰高血糖素反应正常化，在患有糖耐量受损和2型（非胰岛素依赖型）糖尿病的肥胖高胰岛素血症患者中，精氨酸输注期间需要4.2 +/- 0.7和3.8 +/- 0.5 IU的胰岛素剂量。分别这使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3至4倍。此外，我们阐明了正常化、胰岛素作用和/或血糖波动的影响是否有助于这些患者对精氨酸的过度胰高血糖素反应正常化。当以与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而不输注胰岛素时，将血糖钳夹。结果，无论是否存在高血糖症，都实现了夸大的血浆胰高血糖素反应的正常化。这些结果清楚地表明，类似于非肥胖的低胰岛素血症1型（胰岛素依赖性）和2型（非胰岛素依赖性）糖尿病患者，具有葡萄糖耐受不良的肥胖高胰岛素血症患者中对精氨酸输注的过度α细胞应答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中起重要作用。
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.