Mäkimattila S, Hietaniemi K, Kiviluoto T, Timonen T, Yki-Järvinen H
Division of Diabetes, Department of Medicine, University of Helsinki, Helsinki, Finland.
Metabolism. 2001 Sep;50(9):1036-42. doi: 10.1053/meta.2001.25801.
The incidence of diabetes is increased in patients with pancreatic cancer, but the mechanisms underlying this association are not clear. Alterations in beta-cell function, such as formation of amyloid from excessive production of amylin and reduced expression of GLUT2, have been suggested to be possible mechanisms. We compared in vivo secretory responses of amylin and insulin (n = 37) and expression of GLUT2 in pancreata (n = 10) obtained at surgery between diabetic and nondiabetic patients with and without pancreatic tumors. Fourteen had pancreatic adenocarcinoma, 7 had diabetes (duration 6 +/- 3 years) and a pancreatic tumor, 8 had type 2 diabetes (duration 6 +/- 2 years), and 8 were normal subjects. First (0 to 10 minutes) and second (10 to 120 minutes) phase insulin and amylin secretion were characterized using the hyperglycemic clamp technique. Both amylin and insulin concentrations followed a biphasic pattern in nondiabetic subjects. In nondiabetic patients with pancreatic cancer, total, as well as nonglycosylated amylin concentrations, were increased compared with nondiabetic subjects without pancreatic cancer. Both first- and second-phase plasma amylin and serum immunoreactive insulin concentrations were low in all patients with diabetes, ie, both in type 2 diabetes and in those patients with diabetes and pancreatic tumors. At surgery, specimens were obtained for characterization of GLUT2 expression in beta cells, which was unaltered in nondiabetic (n = 7) and diabetic (n = 3) patients. Amyloid staining was similarly negative in diabetic and nondiabetic pancreata independent of pancreatic carcinoma. In conclusion, plasma amylin, but not insulin concentrations, are increased in nondiabetic patients with pancreatic cancer, but low in all patients with diabetes. These data support the potential of using an increase in the ratio of circulating amylin to insulin as a marker for pancreatic cancer in nondiabetic patients.
胰腺癌患者中糖尿病的发病率升高，但其潜在机制尚不清楚。有人提出，β细胞功能改变，如胰岛淀粉样多肽过度产生形成淀粉样蛋白以及葡萄糖转运蛋白2（GLUT2）表达降低，可能是潜在机制。我们比较了糖尿病和非糖尿病且有无胰腺肿瘤的患者在手术时获取的胰岛淀粉样多肽和胰岛素的体内分泌反应（n = 37）以及胰腺中GLUT2的表达（n = 10）。14例患有胰腺腺癌，7例患有糖尿病（病程6±3年）且有胰腺肿瘤，8例患有2型糖尿病（病程6±2年），8例为正常受试者。采用高血糖钳夹技术对胰岛素和胰岛淀粉样多肽分泌的第一阶段（0至10分钟）和第二阶段（10至120分钟）进行了表征。在非糖尿病受试者中，胰岛淀粉样多肽和胰岛素浓度均呈双相模式。与无胰腺癌的非糖尿病受试者相比，患有胰腺癌的非糖尿病患者中，总胰岛淀粉样多肽浓度以及非糖基化胰岛淀粉样多肽浓度均升高。在所有糖尿病患者中，即2型糖尿病患者以及患有糖尿病和胰腺肿瘤的患者中，第一阶段和第二阶段血浆胰岛淀粉样多肽以及血清免疫反应性胰岛素浓度均较低。手术时获取标本以表征β细胞中GLUT2的表达，在非糖尿病患者（n = 7）和糖尿病患者（n = 3）中其表达未改变。无论是否患有胰腺癌，糖尿病和非糖尿病胰腺中的淀粉样蛋白染色均同样为阴性。总之，患有胰腺癌的非糖尿病患者血浆胰岛淀粉样多肽浓度升高，但胰岛素浓度不升高，而所有糖尿病患者的血浆胰岛淀粉样多肽浓度均较低。这些数据支持将循环中胰岛淀粉样多肽与胰岛素的比值升高作为非糖尿病患者胰腺癌标志物的可能性。
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