Administration of branched-chain amino acids reduces the diabetogenic effect of streptozotocin in rats.
1. Previous work has shown that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet and that plasma valine, leucine and isoleucine concentrations are markedly elevated in rats adapted to the high-protein diet. 2. To test the possibility that these branched-chain amino acids play a role in the beneficial effects of the high-protein diet, rats fed the control balanced diet were injected intraperitoneally with mixtures of valine, leucine and isoleucine (0.25 or 0.50 g/kg body weight of each amino acid), or with each of these amino acids separately (0.50 g/kg), 15 min before streptozotocin administration (40 mg/kg, intravenously). Arginine (0.50 g/kg) was administered in one experiment. Control animals received equal volumes of saline. 3. Rats previously injected with the amino acid mixtures showed a partial but significant reduction of diabetes severity as indicated by lower plasma glucose levels, higher rates of body weight gain and greater amounts of epididymal and retroperitoneal fat. No protection was observed after the administration of either valine, isoleucine, leucine or arginine. 4. These data suggest that the elevated levels of plasma branched-chain amino acids may account at least in part for the initial protective effect of high-protein diets against streptozotocin beta-cytotoxicity when the cells are first exposed to the drug.
D000597:Amino Acids, Branched-Chain / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D004032:Diet; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000037:antagonists & inhibitors*
D000597:Amino Acids, Branched-Chain; D013311:Streptozocin