Effects of berberine on skeletal muscle protein metabolism in db/db mice and study of its mechanism / 中华内分泌代谢杂志

ABSTRACT

ObjectiveTo study the effect of berberine on diabetes or insulin resistance accompanied with reduction of skeletal moscle and wasting in db/db mice.Methods db/db mouse-a model of diabetes/insulin-resistance was studied,with the wild type mouse as control.After being treated with berberine ( 5 mg · kg-1 · d-1 ) for 3 weeks,the muscle size of tibia anterior (TA) of the animals was measured after staining with laminine/Hyosin Heavy chain-Slow using immunochemistry,then observed under fluorescent microscope and calculated with software.The rate of [ 14 C ] -Phenalanine incorporation into the uuscle was measured to analyze the protein synthesis,and the [ 3 H ] -Tyrosine released into the medium was determined in order to analyze protein degradation.The mRNA expressions of muscle atrophy Fbox-1 ( Atrogin-1 ) and muscle ring finger-1 ( MuRF-1 ) were measured by Northern blot.Results With berberine treatment,blood glucose and fat levels were lowered [ ( 18.55 ± 3.79 vs 26.32 ± 4.02 ) mmol/L,P＜0.01 ; ( 2.75 ± 0.30 vs 3.77 ± 0.52 ) g,P＜0.05 ],but tibia anterior muscle weight/length ratio and cross-section area were decreased,rates of protein synthesis in isolated muscles of db/db mice were decreased by 18％ -22％,and the rates of degradation were significantly raised by 24％ -26％ after berberine treatment.There also was increased the transcription and translation of Atrogin-1 and MuRF-1,accompanied with decreased eukaryotic initiation factor 3 subunit (eIF3-f)protein level simultaneously. ConclusionBerberine improves hyperglycemia and insulin resistance by down-regulating blood sugar and body fat,but it causes reduced protein synthesis and minimally enhanced protein degradation.The mechanism might be related to berberine-induced up-regulating Atrogin-1 、MurF-1 and down-regulating eIF3-f.