ISLET AMYLOID POLYPEPTIDE IN PATIENTS WITH PANCREATIC-CANCER AND DIABETES

Background. The diabetes mellitus that occurs in patients with pancrea tic cancer is characterized by marked insulin resistance that declines after tumor resection. Islet amyloid polypeptide (IAPP), a hormonal f actor secreted from the pancreatic beta cells, reduces insulin sensiti vity in vivo and glycogen synthesis in vitro. In this study, we examin ed the relation between IAPP and diabetes in patients with pancreatic cancer. Methods. We measured IAPP in plasma from 30 patients with panc reatic cancer, 46 patients with other cancers, 23 patients with diabet es, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger R NA were studied in pancreatic cancers, pancreatic tissue adjacent to c ancers, and normal pancreatic tissue. Results. Plasma IAPP concentrati ons were elevated in the patients with pancreatic cancer as compared w ith the normal subjects (mean [+/-SD], 22.3+/-13.6 vs. 8.0+/-5.0 pmol per liter; P<0.001), normal in the patients with other cancers, and no rmal or low in the patients with diabetes. Among the patients with pan creatic cancer, the concentrations were 25.0+/-8.7 pmol per liter in t he 7 patients with diabetes who required insulin, 31.4+/-12.6 pmol per liter in the 11 patients with diabetes who did not require insulin, a nd 12.2+/-2.4 pmol per liter in the 9 patients with normal glucose tol erance (3 patients had impaired glucose tolerance; their mean plasma I APP concentration was 11.7+/-5.5 pmol per liter). Plasma IAPP concentr ations decreased after surgery in the seven patients with pancreatic c ancer who were studied before and after subtotal pancreatectomy (28.9/-16.4 vs. 5.6+/-3.4 pmol per liter, P = 0.01). Pancreatic cancers con tained IAPP, but the concentrations were lower than in normal pancreat ic tissue (17+/-16 vs. 183+/-129 pmol per gram, P<0.001). In samples f rom the patients with both pancreatic cancer and diabetes, immunostain ing for IAPP was reduced in islets of pancreatic tissue surrounding th e tumor; in situ hybridization studies suggested that transcription oc curred normally in these islets. Conclusions. Plasma IAPP concentratio ns are elevated in patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin resistance, its overproduction may contri bute to the diabetes that occurs in these patients.