Rickels Michael R, Schutta Mark H, Mueller Rebecca, Markmann James F, Barker Clyde F, Naji Ali, Teff Karen L
Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6149, USA.
Diabetes. 2005 Nov;54(11):3205-11. doi: 10.2337/diabetes.54.11.3205.
Islet transplantation can eliminate severe hypoglycemic episodes in patients with type 1 diabetes; however, whether intrahepatic islets respond appropriately to hypoglycemia after transplantation has not been fully studied. We evaluated six islet transplant recipients, six type 1 diabetic subjects, and seven nondiabetic control subjects using a stepped hyperinsulinemic-hypoglycemic clamp. Also, three islet transplant recipients and the seven control subjects underwent a paired hyperinsulinemic-euglycemic clamp. In response to hypoglycemia, C-peptide was similarly suppressed in islet transplant recipients and control subjects and was not detectable in type 1 diabetic subjects. Glucagon was significantly more suppressed in type 1 diabetic subjects than in islet transplant recipients (P < 0.01), although the glucagon in islet transplant recipients failed to activate as in the control subjects (P < 0.01). Pancreatic polypeptide failed to activate in both type 1 diabetic subjects and islet transplant recipients compared with control subjects (P < 0.01). In islet transplant recipients, glucagon was suppressed normally by hyperinsulinemia during the euglycemic clamp and was significantly greater during the paired hypoglycemic clamp (P < 0.01). These results suggest that after islet transplantation and in response to insulin-induced hypoglycemia, endogenous insulin secretion is appropriately suppressed and glucagon secretion may be partially restored.
胰岛移植可消除1型糖尿病患者严重的低血糖发作；然而，移植后肝内胰岛对低血糖的反应是否适当尚未得到充分研究。我们使用逐步高胰岛素-低血糖钳夹技术评估了6名胰岛移植受者、6名1型糖尿病受试者和7名非糖尿病对照受试者。此外，3名胰岛移植受者和7名对照受试者接受了配对高胰岛素-正常血糖钳夹。在低血糖反应中，胰岛移植受者和对照受试者的C肽同样受到抑制，而在1型糖尿病受试者中未检测到C肽。1型糖尿病受试者的胰高血糖素抑制程度明显高于胰岛移植受者（P < 0. 01），尽管胰岛移植受者的胰高血糖素未能像对照受试者那样激活（P < 0.01）。与对照受试者相比，1型糖尿病受试者和胰岛移植受者的胰多肽均未激活（P < 0.01）。在胰岛移植受者中，正常血糖钳夹期间高胰岛素血症可正常抑制胰高血糖素，而在配对低血糖钳夹期间胰高血糖素明显升高（P < 0.01）。这些结果表明，胰岛移植后，在胰岛素诱导的低血糖反应中，内源性胰岛素分泌受到适当抑制，胰高血糖素分泌可能部分恢复。
