[Frontiers in Bioscience 2, d271-282, June 1, 1997]
Reprints
PubMed
CAVEAT LECTOR



Table of Conents
 Previous Section   Next Section

THE ROLE OF LANGERHANS ISLETS IN PANCREATIC DUCTAL ADENOCARCINOMA
Parviz M. Pour

The UNMC/Eppley Cancer Center, University of Nebraska Medical Center, Omaha, NE

Received 5/6/97 Accepted 6/2/97

7. EFFECT OF EXOGENOUS INSULIN ON PANCREATIC ADENOCARCINOMA INDUCTION

The assumption that the deficiency of insulin with its growth promoting action could be the underlying mechanism of the induction of pancreatic cancer could not be confirmed in an experiment (59). When streptozotocin and BOP- treated hamsters received therapeutic daily insulin doses for life, the tumor-protective effect of streptozotocin could not be changed. Strikingly, even fewer animals treated with insulin developed pancreatic tumors than those in the streptozotocin-BOP-treated group (59). Although streptozotocin­treated hamsters recovered from diabetes after 70 days, those treated with insulin remained hyperglycemic and showed a sustained atrophy of their pancreatic islets, which could well explain the very low incidence of pancreatic cancer in this group. Nevertheless, the results indicated that the preventive effect of streptozotocin on pancreatic cancer induction is unrelated to insulin, or that the action of insulin on tumor induction and growth is local and perhaps paracrine, i.e., a direct feedback between carcinogen-initiated cells and intact b-cells is required. This assumption was supported by a study in genetically diabetic and non-diabetic strains of Chinese hamsters.Although non-diabetic hamsters with normal and intact islets developed pancreatic tumors in response to treatment with BOP, the diabetic strains with atrophic islets were resistant to the tumorigenic action of the agent (60). If intact islet cells were in fact essential for the induction of exocrine pancreatic tumors, stimulation of islet regeneration and neogenesis (nesidioblastosis) would enhance the development of pancreatic cancer. This hypothesis was verified in a recent study, where the nesidioblastosis model of Rosenberg et al. was used. These investigators have shown that wrapping a segment of the hamster pancreas with a cellophane strip profoundlystimulated islet neogenesis around the wrapped area (61) to the extent that it cured the streptozotocin-induced diabetes (62). When hamsters with the wrapped pancreata were treated with BOP, significantly more tumors developed in the small wrapped region than in any other areas of the pancreas (63). However, the interpretation of the experiments performed in two independent laboratories differed significantly. Whereas Rosenberg et al. claimed that the tumors derive from ductal epithelium (64), our own results pointed to the derivation of most tumors from islets (63). Development of many ca in situ within islets and the immunoreactivity of some cancer cells with anti-insulin were reasons for our interpretation.