PANCREATIC-CANCER IN RATS AND HAMSTERS DOES NOT INDUCE IAPP-RELATED HYPERGLYCEMIA

Many patients with exocrine pancreatic cancer develop diabetes mellitu s due to insulin resistance. This may relate to concurrent over-produc tion of islet amyloid polypeptide (IAPP) by the pancreatic beta cells. We investigated the effects of pancreatic cancer on circulating IAPP and glucose homeostasis in azaserine-treated rats (developing acinar p ancreatic tumours) and BOP-treated hamsters (developing ductular pancr eatic tumours). Glucose, insulin and IAPP levels in plasma were neithe r affected in azaserine-only treated vats nor in animals with enhanced carcinogenesis after chronic caerulein treatment. Azaserine-treated r ats on a high-fat diet had decreased insulin levels and enhanced IAPP/ insulin ratios in plasma, without hyperglycaemia. All BOP-treated hams ters showed pancreatic carcinogenesis at 6 months post-treatment. Supr anormal plasma glucose levers in animals on a low-fat diet were the on ly change observed. After a second 6-month period, subnormal plasma gl ucose levels, at least 4-fold decreased plasma insulin and up to 2-fol d decreased plasma IAPP levels were present in all hamsters. Remarkabl y, both in azaserine-treated rats on high-fat and in BOP-treated hamst ers, decreased insulin levels and elevated IAPP/insulin ratios are not associated with hyperglycaemia. In contrast to humans with pancreatic cancer, IAPP overproduction and hyperglycaemia do not develop in rats and hamsters with (pre-)neoplastic pancreatic lesions. (C) 1997 Wiley -Liss, Inc.