Summary
Previous studies showed that the diabetogenic action of streptozotocin is reduced in rats adapted to a high-protein, carbohydrate-free diet, that have markedly elevated plasma concentrations of valine, leucine and isoleucine. In order to test the role of these branched chain amino acids (BCAA) in the beneficial effects of the high-protein diets, rats adapted (15 days) either to a balanced synthetic diet, or to the same diet supplemented with BCAA were injected with streptozotocin (STZ) (40 mg/kg body weight) and maintained on the same diets after drug injection. Rats previously fed the BCAA enriched diet showed a partial but significant reduction in the severity of diabetes, as indicated by higher rates of body weight gain, lower food and water intake, lower excretion of glucose and higher serum insulin levels. Rats previously fed the control diet for 14 days, but transferred to the BCAA diet 3 days after STZ injection, also showed reduced severity of diabetes, as indicated by rates of body weight gain, water and food ingestion, glucose and insulin levels. The data suggest that the increased supply of BCAA is responsible, at least in part, for the previously reported beneficial effects of high-protein diets in rats with STZ-induced diabetes.
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Aftring R. P., Manos P. N., Buse M. G.: Catabolism of branched-chain amino acids by diaphragm muscles of fasted and diabetic rats — Metabolism34, 702, 1985.
Aoki T. T., Assal J.-Ph., Manzano F. M., Kozak G. P., Cahill G. E. Jr: Plasma and cerebrospinal fluid amino acid levels in diabetic ketoacidosis before and after corrective therapy — Diabetes24, 463, 1975.
Blackburn G. L., Moldawer L. L., Usui S., Bothe A., O’Keefe S. J. D., Bistrian B. R.: Branched chain amino acid administration and metabolism during starvation, injury and infection — Surgery86, 307, 1979.
Bloxam D. L.: Nutritional aspects of amino acid metabolism. 3. The effects of diabetes on blood and liver amino acid concentrations in the rat — Brit. J. Nutr.27, 249, 1972.
Buse M. G., Reid M.: Leucine, a possible regulator of protein turnover in muscle — J. clin. Invest.58, 1250, 1975.
Carlsten A., Hallgren B., Jagenburg R., Svanborg A., Werkö L.: Amino acids and free fatty acids in plasma in diabetes. I. The effect of insulin on the arterial levels — Acta med. scand.179, 361, 1966.
Eisenbarth G. S.: Type 1 diabetes mellitus. A chronic autoimmune disease — New Engl. J. Med.314, 1360, 1986.
Eisenstein A. B., Strack I., Galo Torres H., Georgiadis A., Milner O. N.: Increased glucagon secretion in protein fed rats: lack of relationship to plasma amino acids — Amer. J. Physiol.236, E20, 1979.
Eizirik D. L.: Doctoral thesis. University of São Paulo, Ribeirão Preto, Brasil, 1984.
Eizirik D. L., Boschero A. C., Migliorini R. H.: Previous adaptation to a high-protein diet protects against streptozotocin-induced inhibition of insulin release from isolated rat islets — Braz. J. med. biol. Res.18, 233, 1985.
Eizirik D. L., Kettelhut I. C., Migliorini R. H.: Administration of branched chain amino acids reduces the diabetogenic effect of streptozotocin in rats — Braz. J. med. biol. Res.20, 137, 1987.
Eizirik D. L., Migliorini R. H.: Reduced diabetogenic effect of streptozotocin in rats previously adapted to a high-protein, carbohydrate-free diet — Diabetes33, 383, 1984.
Eizirik D. L., Sandler S.: The partial protective effect of branched chain amino acids against streptozotocin-induced cytotoxicity to mouse pancreatic isletsin vitro — Pharmacol. Toxicol.61, 320, 1987.
Eizirik D. L., Tze W. J., Tai J., Migliorini R. H.: Effect of a high-protein diet on the evolution of diabetes in streptozotocin-induced and spontaneously diabetic BB Wistar rats — Acta diabetol. lat.23, 107, 1986.
Felig P., Wahrén J., Sherwin R., Palaiologos G.: Amino acid and protein metabolism in diabetes mellitus — Arch. intern. Med.137, 507, 1977.
Frayser R., Buse M. G.: Branched chain amino acid metabolism in the retina of diabetic rats — Diabetologia14, 171, 1978.
Freund H., Yoshimura N., Fischer J. E.: The effect of branched chain amino acids and hypertonic glucose infusions on postinjury catabolism in the rat — Surgey87, 401, 1980.
Fulks R. M., Li J. B., Goldberg A. L.: Effects of insulin, glucose and amino acids on protein turnover in rat diaphragm — J. biol. Chem.250, 280, 1975.
Giroix M. H., Portha B., Kergoat M., Bailbe D., Picon L.: Glucose insensitivity and amino acid hypersensitivity of insulin release in rats with non-insulin dependent diabetes. A study with the perfused pancreas — Diabetes32, 445, 1983.
Goldberg A. L., Chang T. W.: Regulation and significance of amino acid metabolism in skeletal muscle — Fed. Proc.37, 2301, 1978.
Grill V., Herberg L.: Glucose and arginine-induced insulin and glucagon response from the isolated perfused pancreas of the BB-Wistar diabetic rat. Evidence for selective impairment of glucose regulation — Acta endocrinol. (Kbh.)102, 561, 1983.
Harper A. E., Benevenga N. J., Wohlueter R. M.: Effects of ingestion of disproportionate amounts of amino acids — Physiol. Rev.50, 428, 1970.
Hawk P. B., Oser B. L., Summerson W. H.: Practical physiological chemistry. 12th ed. Blakiston Co., New York, 1947; p. 860.
Kettelhut I. C., Foss M. C., Migliorini R. H.: Glucose homeostasis in a carnivorous animal (cat) and in rats fed a high-protein diet — Amer. J. Physiol.239, R437, 1980.
Leiter E. H., Coleman D. L., Eisenstein A. B., Strack I.: Dietary control of pathogenesis in C57 BL/KsJdb/db diabetes mince — Metabolism30, 554, 1981.
Morgan C. R., Lazarow A.: Immunoassay of insulin: two antibody systems. Plasma insulin levels of normal, subdiabetic and diabetic rats — Diabetes12, 115, 1963.
Rémésy C., Demigné C., Aufrère J.: Inter-organ relationship between glucose, lactate and amino acids in rats fed high-carbohydrate or high-protein diets — Biochem. J.170, 321, 1978.
Schäfer G., Schätz H.: Long-term effects of leucine and arginine on B-cell function of cultivated pancreatic islets — J. Endocrinol.91, 255, 1981.
Siegel E. G., Trapp V. E., Wollheim C. B., Renold A. E., Schmidt F. H.: Beneficial effects of low-carbohydrate-high-protein diets in long term diabetic rats — Metabolism29, 421, 1980.
Spackman D. A., Stein W. H., Moore S.: Automatic recording apparatus for use in chromatography of amino acids — Analyt. Chem.30, 1190, 1958.
Umpleby A. M., Boroujerdi M. A., Brown P. M., Carson E. R., Sönksen P. H.: Branched chain amino acid metabolism in diabetes — Diabetes31 (Suppl. 2), 63 A, 1982; abstract # 251.
Vannini P., Marchesini G., Forlani G., Angiolini A., Ciavarella A., Zoli M., Pisi E.: Branched-chain amino acids and alanine as indices of the metabolic control in type 1 (insulin-dependent) and type 2 (non-insulin dependent) diabetic patients — Diabetologia22, 217, 1982.
Zatz R., Meyer T. W., Rennke H. G., Brenner B. M.: Predominance of hemodynamic rather than metabolic factors in the pathogenesis of diabetic glomerulopathy — Proc. nat. Acad. Sci. (Wash.)82, 5963, 1985.
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Eizirik, D.L., Germano, C.M. & Migliorini, R.H. Dietetic supplementation with branched chain amino acids attenuates the severity of streptozotocin-induced diabetes in rats. Acta diabet. lat 25, 117–126 (1988). https://doi.org/10.1007/BF02581375
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DOI: https://doi.org/10.1007/BF02581375