Sakai T, Ohneda A, Nihei J, Kobayashi T
Tohoku J Exp Med. 1982 Dec;138(4):427-40. doi: 10.1620/tjem.138.427.
In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects. The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively. Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.
为阐明胰岛素分泌机制，我们对正常受试者以及糖尿病、肝硬化、慢性肾炎或胰岛素瘤患者血浆中胰岛素（IRI）和C肽（CPR）对各种刺激的反应进行了研究。轻度和中度糖尿病组血浆IRI和CPR对口服葡萄糖负荷的反应不如正常对照组明显。重度糖尿病组的IRI和CPR对口服葡萄糖均无反应。肝硬化患者的IRI和CPR反应增强且延迟，CPR/IRI比值降低，表明IRI对葡萄糖反应显著。相比之下，慢性肾炎患者仅CPR显著升高。胰岛素瘤患者葡萄糖负荷后血浆IRI和CPR均升高。在对葡萄糖的反应中，正常对照组和各类疾病患者的IRI和CPR峰值之间大约有30分钟的延迟时间。输注精氨酸后，正常受试者和中度糖尿病患者的血浆IRI和CPR升高。在正常受试者中，血浆IRI分别在服用甲苯磺丁脲和胰高血糖素后6分钟和3分钟达到峰值，这两种物质可使B细胞胰岛素急剧升高。然而，糖尿病患者血浆IRI和CPR变化极小，而胰岛素瘤患者血浆IRI和CPR反应增强。在分析血浆IRI和CPR对甲苯磺丁脲或胰高血糖素的反应时，正常受试者存在超过10分钟的延迟时间。本研究证实了胰岛素分泌过程中B细胞同时释放C肽。此外，提示胰岛素和C肽分别主要在肝脏和肾脏中代谢。此外，IRI和CPR对甲苯磺丁脲或胰高血糖素反应峰值之间较长的延迟时间不一定表明胰岛素和C肽从B细胞同时释放，而是后者释放延迟。
