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Clofibrate‐Induced Reduction of Plasma Branched‐Chain Amino Acid Concentrations Impairs Glucose Tolerance in Rats
Author(s) -
Kadota Yoshihiro,
Kazama Shunsuke,
Bajotto Gustavo,
Kitaura Yasuyuki,
Shimomura Yoshiharu
Publication year - 2012
Publication title -
journal of parenteral and enteral nutrition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.935
H-Index - 98
eISSN - 1941-2444
pISSN - 0148-6071
DOI - 10.1177/0148607111414578
Subject(s) - clofibrate , medicine , endocrinology , reduction (mathematics) , chemistry , plasma glucose , parenteral nutrition , diabetes mellitus , geometry , mathematics
It has been reported that branched‐chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched‐chain α‐keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched‐chain α‐keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate‐treated rats than in control rats. This impaired glucose tolerance in the clofibrate‐treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.