Insulin--carcinogen or mitogen? Preclinical and clinical evidence from prostate, breast, pancreatic, and colorectal cancer research.
Diabetes mellitus is a chronic disease that affects > 23.6 million Americans, and occurs when the body is unable to produce or becomes resistant to endogenous insulin. This alteration of insulin's action reduces adequate utilization of glucose transporter type 4 (GLUT4) receptors, which are responsible for cellular glucose uptake. Thus, exogenous administration of human insulin and insulin analogs is an important modality used to reduce morbidity and mortality in both type 1 and type 2 diabetes. According to 2007 estimates, 27% of all patients with diabetes use some form of insulin therapy. The increasing utilization of insulin has become a cause for concern because findings from several observational trials have suggested an association with an increased risk of developing cancer. To help elucidate the potential interplay between insulin use and cancer, we searched PubMed and MEDLINE to identify articles that assessed the carcinogenic and/or mitogenic potential of diabetes treatments, focusing on insulin specifically. Data from our review suggest that insulin analogs, particularly insulin glargine, may play more of a mitogenic than a carcinogenic role in association with different types of cancer, suggesting an amplified rate of existing tumor growth in the presence of insulin analogs. Evidence for insulin-induced mitogenicity appears to be most prevalent in prostate, breast, pancreatic, and colorectal cancers. In conclusion, the positive effects of insulin therapy on reducing morbidity and mortality in diabetes greatly outweigh the risks at this time. However, clinicians must be diligent in both screening for new cancers in patients receiving insulin and in monitoring for tumor growth or maintenance of remission in patients with existing cancers.
Call
Rosemary
R
University of Mississippi School of Pharmacy, Jackson, MS 39216, USA.
Grimsley
Molly
M
Cadwallader
Lucy
L
Cialone
Laura
L
Hill
Matt
M
Hreish
Vera
V
King
S Travis
ST
Riche
Daniel M
DM
D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000502:physiology; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D009369:Neoplasms / Q000139:chemically induced* / Q000473:pathology; D011358:Product Surveillance, Postmarketing; D017451:Receptors, Somatomedin / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D017451:Receptors, Somatomedin; D000069036:Insulin Glargine