Prevention of pancreatic cancer induction in hamsters by metformin.
OBJECTIVE
Our previous study suggested that the known promotional effect of a high fat diet, which in hamsters induces peripheral insulin resistance, is related to a compensatory proliferation of islet cells. The present study was to examine whether the prevention of islet cell proliferation can inhibit the promotional effect of a high-fat diet in pancreatic carcinogenesis.


METHODS
Two groups of high fat-fed hamsters were used. One group received Metformin in drinking water for life (HF+Met group), and the other group served as a control (HF group). At the time when the normalization of the plasma insulin level was expected, all hamsters were treated with the pancreatic carcinogen, N-nitrosobis-(2-oxopropyl)amine, and the experiment was terminated 42 weeks later.


RESULTS
Although 50% of the hamsters in the high-fat group developed malignant lesions, none was found in the HF+Met group (P < 0.05). Also, significantly more hyperplastic and premalignant lesions, most of which were found within the islets, were detected in the high-fat group (8.6 lesions/hamster) than in the HF+Met group (1.8 lesions/hamster).


CONCLUSIONS
The results lend further support on the significant role of islet cells in pancreatic carcinogenesis and may explain the association between pancreatic cancer and obesity, which is usually associated with peripheral insulin resistance.
The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska 68198-6805, USA.
M B
MB
Schneider
H
H
Matsuzaki
J
J
Haorah
A
A
Ulrich
J
J
Standop
X Z
XZ
Ding
T E
TE
Adrian
P M
PM
Pour
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004041:Dietary Fats / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008647:Mesocricetus; D008687:Metformin / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D004247:DNA; D008687:Metformin; D005947:Glucose