Effect of probucol on development of diabetes mellitus in BB rats.
Insulin-dependent diabetes mellitus (IDDM) results from an inflammatory process leading to destruction of the insulin-producing beta cells of the pancreas. Genetically mediated autoimmune processes are considered the most likely explanation for IDDM in humans, while viral infections, toxic agents, nutritional alterations and stress are also considered possibilities. The precise mechanisms by which autoimmunity, infections, toxins or other agents produce beta cell damage are not known. Toxin-induced diabetes in animals can be prevented by antioxidant therapy, while an agent that inhibits hydroxyl radical formation, desferrioxamine, extends the survival time of free allotypic islets in nonobese diabetic mice. The BB/W rat develops IDDM secondary to a pervasive autoimmune defect. This well-studied animal model develops IDDM with a highly predictable frequency and timing. This study describes the effects of the potent antioxidant, probucol, on the development of diabetes in BB rats by introducing it into standard rat chow at a 1% concentration at the time of weaning, and continuing this feeding schedule through 160 days of life. Control rats from split litters received standard chow only. Diabetes developed in 86.2% of the control rats at a mean age of 90.4 days. Probucol administration was associated with a reduction to 62% and a delay in diabetes diagnosis to 99.6 days. These very preliminary results suggest that probucol may be altering the inflammatory process, resulting in beta cell destruction in these genetically diabetes-prone rats.
Drash
A L
AL
University of Pittsburgh, School of Medicine, Department of Pediatrics, Children's Hospital, Pennsylvania 15213.
Rudert
W A
WA
Borquaye
S
S
Wang
R
R
Lieberman
I
I
D000206:Actuarial Analysis; D000367:Age Factors; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D005260:Female; D008297:Male; D010636:Phenols / Q000627:therapeutic use*; D011341:Probucol / Q000627:therapeutic use*; D051381:Rats; D011913:Rats, Inbred BB
D010636:Phenols; D011341:Probucol