Pancreatic cancer in rats and hamsters does not induce IAPP-related hyperglycaemia

Int J Cancer. 1997 Aug 7;72(4):637-41. doi: 10.1002/(sici)1097-0215(19970807)72:4<637::aid-ijc15>3.0.co;2-8.

Abstract

Many patients with exocrine pancreatic cancer develop diabetes mellitus due to insulin resistance. This may relate to concurrent over-production 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 pancreatic tumours) and BOP-treated hamsters (developing ductular pancreatic tumours). Glucose, insulin and IAPP levels in plasma were neither affected in azaserine-only treated rats nor in animals with enhanced carcinogenesis after chronic caerulein treatment. Azaserine-treated rats on a high-fat diet had decreased insulin levels and enhanced IAPP/insulin ratios in plasma, without hyperglycaemia. All BOP-treated hamsters showed pancreatic carcinogenesis at 6 months post-treatment. Supranormal plasma glucose levels in animals on a low-fat diet were the only change observed. After a second 6-month period, subnormal plasma glucose levels, at least 4-fold decreased plasma insulin and up to 2-fold decreased plasma IAPP levels were present in all hamsters. Remarkably, both in azaserine-treated rats on high-fat and in BOP-treated hamsters, decreased insulin levels and elevated IAPP/insulin ratios are not associated with hyperglycaemia. In contrast to humans with pancreatic cancer, IAPP over-production and hyperglycaemia do not develop in rats and hamsters with (pre-)neoplastic pancreatic lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / blood*
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Carcinogens
  • Cricetinae
  • Dietary Fats / adverse effects
  • Disease Models, Animal
  • Homeostasis
  • Hyperglycemia / blood*
  • Hyperglycemia / etiology*
  • Insulin / blood
  • Islet Amyloid Polypeptide
  • Male
  • Mesocricetus
  • Organ Size / drug effects
  • Pancreas / anatomy & histology
  • Pancreas / drug effects
  • Pancreatic Neoplasms / blood*
  • Pancreatic Neoplasms / chemically induced
  • Pancreatic Neoplasms / complications*
  • Precancerous Conditions / blood*
  • Precancerous Conditions / chemically induced
  • Rats
  • Rats, Wistar

Substances

  • Amyloid
  • Blood Glucose
  • Carcinogens
  • Dietary Fats
  • Insulin
  • Islet Amyloid Polypeptide