Prevention of proliferative changes of forestomach mucosa by blood glucose control with insulin in alloxan-induced diabetic rats.

Abstract

Diabetes mellitus is one of the risk factors for carcinogenesis. Recently we reported that alloxan induces squamous cell carcinoma (SCC) with coincidental inflammation, bacteria/fungal infections, and a severe diabetic condition. The present study was conducted to examine the effects of blood glucose control with insulin on the proliferative changes of the forestomach in alloxan-induced diabetic rats. Male 15-week-old WBN/Kob rats were divided into a control group of non-treated rats with naturally occurring diabetes after 40 weeks of age (non-treated group), alloxan-induced diabetic rats (AL group), and alloxan-induced diabetic rats given insulin implant treatment (AL + In group). The animals were sacrificed at 90 weeks of age for histopathologic examination. The blood glucose and urinary glucose level of the AL + In group fluctuated variously from high to normal levels compared with a constantly high level of AL (for 75 weeks) as well as in the non-treated group (for 50 weeks). The mucosal hyperplasia in the forestomach developed in 88.2% of the AL group and 37.5% of the non-treated group, but in only 10.0% of the AL + In group. SCC was only detected in 23.5% of the AL group. Hyperplastic changes were constantly accompanied by inflammation and fungal/bacterial infections in the AL and non-treated groups, whereas inflammation and fungal infection were completely suppressed in the AL + In group. These findings demonstrate that blood glucose control suppressed neoplastic changes in alloxan-induced diabetic rats. We postulate that inflammation together with bacterial/fungal infections under prolonged severe diabetic conditions play a pivotal role in carcinogenesis.

• Authors: Tomoya Sano, Kiyokazu Ozaki, Yasushi Kodama, Tetsuro Matsuura, Isao Narama
• Journal: Cancer science (Cancer Sci) Vol. 100 Issue 4 Pg. 595-600 (Apr 2009) ISSN: 1349-7006 [Electronic] England
• PMID: 19154414 (Publication Type: Journal Article)

Chemical References

• Blood Glucose
• Hypoglycemic Agents
• Insulin
• Proliferating Cell Nuclear Antigen
• Alloxan

Topics

• Alloxan (toxicity)
• Animals
• Blood Glucose (analysis)
• Cell Proliferation (drug effects)
• Diabetes Mellitus, Experimental (blood, drug therapy, physiopathology)
• Glycosuria
• Hypoglycemic Agents (blood, pharmacology, therapeutic use)
• Immunohistochemistry
• Insulin (blood, pharmacology, therapeutic use)
• Intestinal Mucosa (drug effects, pathology)
• Male
• Proliferating Cell Nuclear Antigen (metabolism)
• Rats
• Rats, Inbred Strains
• Stomach (physiopathology)