In vivo glucose-stimulated amylin secretion is increased in nondiabetic patients with pancreatic cancer.
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.
Mäkimattila
S
S
Division of Diabetes, Department of Medicine, University of Helsinki, Helsinki, Finland.
Hietaniemi
K
K
Kiviluoto
T
T
Timonen
T
T
Yki-Järvinen
H
H
D000230:Adenocarcinoma / Q000150:complications / Q000378:metabolism*; D000682:Amyloid / Q000097:blood / Q000378:metabolism*; D001786:Blood Glucose; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism; D005947:Glucose; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D051273:Glucose Transporter Type 2; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000378:metabolism*; D011237:Predictive Value of Tests; D012016:Reference Values
D000682:Amyloid; D001786:Blood Glucose; D051273:Glucose Transporter Type 2; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D009004:Monosaccharide Transport Proteins; D005934:Glucagon; D005947:Glucose