Islet Amyloid Polypeptide in Patients with Pancreatic Cancer and Diabetes

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Abstract
The diabetes mellitus that occurs in patients with pancreatic cancer is characterized by marked insulin resistance that declines after tumor resection. Islet amyloid polypeptide (IAPP), a hormonal factor secreted from the pancreatic beta cells, reduces insulin sensitivity in vivo and glycogen synthesis in vitro. In this study, we examined the relation between IAPP and diabetes in patients with pancreatic cancer. We measured IAPP in plasma from 30 patients with pancreatic cancer, 46 patients with other cancers, 23 patients with diabetes, and 25 normal subjects. IAPP immunoreactivity and IAPP messenger RNA were studied in pancreatic cancers, pancreatic tissue adjacent to cancers, and normal pancreatic tissue. Plasma IAPP concentrations were elevated in the patients with pancreatic cancer as compared with 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 normal or low in the patients with diabetes. Among the patients with pancreatic cancer, the concentrations were 25.0 ±8.7 pmol per liter in the 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, and 12.2 ±2.4 pmol per liter in the 9 patients with normal glucose tolerance (3 patients had impaired glucose tolerance; their mean plasma IAPP concentration was 11.7 ±5.5 pmol per liter). Plasma IAPP concentrations decreased after surgery in the seven patients with pancreatic cancer 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 contained IAPP, but the concentrations were lower than in normal pancreatic tissue (17 ±16 vs. 183 ±129 pmol per gram, P<0.001). In samples from the patients with both pancreatic cancer and diabetes, immunostaining for IAPP was reduced in islets of pancreatic tissue surrounding the tumor; in situ hybridization studies suggested that transcription occurred normally in these islets. Plasma IAPP concentrations are elevated in patients with pancreatic cancer who have diabetes. Since IAPP may cause insulin resistance, its overproduction may contribute to the diabetes that occurs in these patients.