糖尿病患者におけるアルギニン負荷時のグルカゴン過剰分泌反応の正常化に関する研究:人工膵島システムの応用
スポンサーリンク
概要
- 論文の詳細を見る
An exaggerated rise in plasma glucagon (IRG) during stimulation by intravenous arginine infusion is one of the characteristic abnormalities in diabetes mellitus. Since the administration of insulin lowers the exaggerated IRG responses to arginine, this abnormality is thought to be secondary to insulin deficiency. However, in previous reports the doses and patterns of insulin administration were variable, and the normalization of glucose and plasma insulin profiles during arginine infusion was not achieved. Thus the effect of each factor to normalize exaggerated IRG responses has not been clarified.<BR>In the artificial endocrine pancreas (AEP) that we originally developed, the perfect physiological normalization of blood glucose and plasma insulin profiles can be achieved in diabetes mellitus, and in addition, optimal glycemic clamp becomes possible with the operation of glucose infusion algorithm. To clarify whether the physiological blood glucose and plasma insulin profiles can normalize the exaggerated IRG responses and to qualify the effect of each of the glycemic excursions and insulin profiles, the following 4 investigations were conducted in each of 7 nonobese noninsulin-dependent diabetes mellitus (NIDDM) patients and 8 insulin-dependent diabetes mellitus (IDDM) patients with the aid of AEP.<BR>Arginine was iv infused into both diabetic groups according to the following protocol : 1) in a hyperglycemic state without insulin infusion, 2) in perfect glycemic control by AEP, 3) in glycemic control by AEP with lower plasma insulin profiles (parameters of insulin in-fusion algorithm were made smaller than 2)), 4) in a hyperglycemic state with physiological plasma insulin profiles (blood glucose was clamped in the same way as 1) with glucose in fusion algorithm by AEP, and insulin infusion obtained in 2) was operated with a preprogrammable insulin infusion pump). The changes in plasma glucagon responses in each experiment were compared with those seen in healthy subjects.<BR>It was revealed that IRG responses were completely normalized in 2) and 4) in both NIDDM and IDDM, of which plasma insulin profiles simulated those of healthy subjects whether hyperglycemia existed or not, but in 1) and 3), in which plasma insulin concentration was not detectable or low, marked hyperresponses of IRG were recognized.<BR>In summary, it is clearly proven with this series of experiments that the exaggerated response of A-cell to arginine in insulin-deficient diabetes mellitus is secondary to insulin deficiency, and its normalization is dependent on physiological insulin concentrations whether hyperglycemia exists or not.
- 日本内分泌学会の論文