Gupta V, Wahoff D C, Rooney D P, Poitout V, Sutherland D E, Kendall D M, Robertson R P
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Diabetes. 1997 Jan;46(1):28-33. doi: 10.2337/diab.46.1.28.
The optimal site for pancreatic islet cell transplantation is presently unclear, although the liver has been the most commonly used. However, glucagon secretion from islets that have been autotransplanted in liver has been reported to be unresponsive to hypoglycemia yet responsive to arginine. To determine whether this selective glucagon secretory defect is related to the intrahepatic site of islet implantation or to the process of transplantation per se, we studied counterregulatory responses to hypoglycemia in dogs with pancreatic islet autotransplantation in the hepatic parenchyma (the intrahepatic [IH] group, n = 9) or the peritoneal cavity (the intraperitoneal [IP] group, n = 9), following total pancreatectomy, and compared them with the responses in normal controls (n = 10). Dogs were subjected to a hypoglycemic hyperinsulinemic (5 mU x kg-1 x min-1) clamp for 90 min under general anesthesia. Arterial glucose concentrations were clamped at 2.7 mmol/l for the final 45 min of the clamp. Immediately following the clamp, glucagon responses to IV arginine (5 g) were also assessed. During hypoglycemia, glucagon responses in the IH group (maximal incremental glucagon = 33 +/- 21 ng/l; glucagon area under curve [AUC] = 713 +/- 1,022 ng x l-1 x min-1) were significantly lower than either the IP (maximal incremental glucagon = 92 +/- 32 ng/l; glucagon AUC = 4,090 +/- 1,600 ng x l-1 x min-1) or control (maximal incremental glucagon = 154 +/- 71 ng/l; glucagon AUC = 6,943 +/- 2,842 ng x l-1 x min-1) group (IH vs. IP group, P < 0.05; control vs. IH group, P < 0.01). Glucagon responses in the IP group did not differ significantly from the control group. Epinephrine responses to hypoglycemia were similar in all groups, whereas neither of the transplanted groups (IH and IP) had pancreatic polypeptide responses. There was a prompt rise in plasma glucagon after intravenous arginine in all groups. These data indicate that glucagon unresponsiveness to hypoglycemia is specific to intrahepatically transplanted islets, rendering the liver a disadvantageous site for optimal alpha-cell function.
目前尚不清楚胰岛细胞移植的最佳部位，尽管肝脏是最常用的部位。然而，据报道，自体移植到肝脏的胰岛分泌的胰高血糖素对低血糖无反应，但对精氨酸有反应。为了确定这种选择性胰高血糖素分泌缺陷是与胰岛植入的肝内部位有关还是与移植过程本身有关，我们研究了全胰切除术后在肝实质内进行胰岛自体移植的犬（肝内[IH]组，n = 9）或腹腔内进行胰岛自体移植的犬（腹腔内[IP]组，n = 9）对低血糖的反调节反应，并将其与正常对照组（n = 10）的反应进行比较。在全身麻醉下，对犬进行90分钟的低血糖高胰岛素（5 mU·kg-1·min-1）钳夹。在钳夹的最后45分钟，将动脉血糖浓度钳制在2.7 mmol/l。钳夹结束后，立即评估胰高血糖素对静脉注射精氨酸（5 g）的反应。在低血糖期间，IH组的胰高血糖素反应（最大胰高血糖素增量 = 33 ± 21 ng/l；胰高血糖素曲线下面积[AUC] = 713 ± 1,022 ng·l-1·min-1）显著低于IP组（最大胰高血糖素增量 = 92 ± 32 ng/l；胰高血糖素AUC = 4,090 ± 1,600 ng·l-1·min-1）或对照组（最大胰高血糖素增量 = 154 ± 71 ng/l；胰高血糖素AUC = 6,943 ± 2,842 ng·l-1·min-1）（IH组与IP组比较，P < 0.05；对照组与IH组比较，P < 0.01）。IP组的胰高血糖素反应与对照组无显著差异。所有组对低血糖的肾上腺素反应相似，而两个移植组（IH组和IP组）均无胰多肽反应。所有组静脉注射精氨酸后血浆胰高血糖素均迅速升高。这些数据表明，胰高血糖素对低血糖无反应是肝内移植胰岛所特有的，这使得肝脏成为不利于α细胞最佳功能的部位。
