Prevention of proliferative changes of forestomach mucosa by blood glucose control with insulin in alloxan-induced diabetic rats.
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.
Sano
Tomoya
T
Department of Pathology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
Ozaki
Kiyokazu
K
Kodama
Yasushi
Y
Matsuura
Tetsuro
T
Narama
Isao
I
D000496:Alloxan / Q000633:toxicity; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D049109:Cell Proliferation / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006029:Glycosuria; D007004:Hypoglycemic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000503:physiopathology
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D018809:Proliferating Cell Nuclear Antigen; D000496:Alloxan