Koivisto V A, Yki-Järvinen H, Hartling S G, Pelkonen R
J Clin Endocrinol Metab. 1986 Nov;63(5):1117-20. doi: 10.1210/jcem-63-5-1117.
To examine possible feedback inhibition of insulin on proinsulin secretion, we measured serum proinsulin levels before and after 120 min of euglycemic hyperinsulinemia (90-100 mU/liter) in 11 normal and 7 obese hyperinsulinemic subjects and 6 patients with beta-cell adenoma (n = 4), carcinoma, or hyperplasia. Baseline proinsulin levels accounted for 19%, 14%, and 56% of the total immunoreactive insulin in the 3 groups, respectively. Compared to normal subjects, baseline proinsulin levels were elevated (P less than 0.02) by 4- and 6-fold in obese subjects and patients with autonomous insulin secretion, respectively, but there was an overlap between the groups. In both normal and obese subjects, hyperinsulinemia suppressed proinsulin secretion by 45-50% (P less than 0.02), whereas no response occurred in the patients. Thus, the 120 min values were clearly different in the patients and the normal or obese subjects. After removal of the adenoma in 4 patients, baseline proinsulin levels and the response to hyperinsulinemia were normalized, but they remained elevated after a partial pancreatectomy or tumor removal in the patients with beta-cell hyperplasia or carcinoma. Thus, proinsulin secretion is under negative feedback control of insulin in both normal man and hyperinsulinemic obese subjects. In patients with insulinoma or beta-cell hyperplasia, this control is lost.
为了研究胰岛素对胰岛素原分泌可能存在的反馈抑制作用，我们在11名正常人和7名肥胖高胰岛素血症患者以及6例患有β细胞腺瘤（n = 4）、癌或增生的患者中，测量了血糖正常的高胰岛素血症（90 - 100 mU/升）120分钟前后的血清胰岛素原水平。在这3组中，基础胰岛素原水平分别占总免疫反应性胰岛素的19%、14%和56%。与正常受试者相比，肥胖受试者和自主胰岛素分泌患者的基础胰岛素原水平分别升高了4倍和6倍（P < 0.02），但各组之间存在重叠。在正常和肥胖受试者中，高胰岛素血症均使胰岛素原分泌抑制了45% - 50%（P < 0.02），而患者无反应。因此，患者与正常或肥胖受试者的120分钟时的值明显不同。4例患者切除腺瘤后，基础胰岛素原水平和对高胰岛素血症的反应恢复正常，但β细胞增生或癌患者行部分胰腺切除术或肿瘤切除后，其水平仍升高。因此，在正常人和高胰岛素血症肥胖受试者中，胰岛素原分泌受胰岛素的负反馈控制。在胰岛素瘤或β细胞增生患者中，这种控制丧失。
