Pancreatic cancer in rats and hamsters does not induce IAPP-related hyperglycaemia.
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.
Oosterwijk
C
C
Department of Internal Medicine, University Hospital Utrecht, The Netherlands.
van Hulst
K L
KL
Visser
C J
CJ
Woutersen
R A
RA
Lips
C J
CJ
van den Tweel
J G
JG
Höppener
J W
JW
D000682:Amyloid / Q000097:blood*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D006224:Cricetinae; D004041:Dietary Fats / Q000009:adverse effects; D004195:Disease Models, Animal; D006706:Homeostasis; D006943:Hyperglycemia / Q000097:blood* / Q000209:etiology*; D007328:Insulin / Q000097:blood; D058228:Islet Amyloid Polypeptide; D008297:Male; D008647:Mesocricetus; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000033:anatomy & histology / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000139:chemically induced / Q000150:complications*; D011230:Precancerous Conditions / Q000097:blood* / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar
D000682:Amyloid; D001786:Blood Glucose; D002273:Carcinogens; D004041:Dietary Fats; D007328:Insulin; D058228:Islet Amyloid Polypeptide