Therapeutic effect of amino acid mixture on type 1 diabetes mellitus with impaired renal methionine reabsorption

Background: The main manifestation of Type 1 diabetes mellitus (T1DM) is insulin insufficiency which eventually leads to body weight loss and a diversity of organ dysfunctions. On the other hand, quercetin (QT) is an antioxidant and an insulin secretagogue. We hypothesize that the amino acid mixture (AAM) preparation and/or AAM+ quercetin(QT) probably could ameliorate these adverse effects. Methods: The STZ-DM-Sprague Dawley rat model was carried out and respectively treated with QT, AAM, and AAM+QT. The relevant physiological and biochemical changes in serum and urinary parameters were examined. Results: T1DM exhibited severe insulin insufficiency, body weight loss, increased kidney/body weight ratio, BUN, creatinine clearance, albuminuria and proteinuria, declined serum albumin and amino acid reabsorption involving methionine, leucine and isoleucine. The control showed severe serinuria (12.0±0.2 mg/mL) (p<0.001). AAM caused valinuria (3.6±0.2 mg/mL), argininuria (6.9±0.2 mg/mL) and histidinuria (6.5±0.1 mg/mL) (p<0.05). T1DM rats revealed hyperglycinuria (21.4±0.2 mg/mL) (p<0.01); AAM alleviated hyperglycinuria (13.7±0.2 mg/mL) (p<0.001) but evoked isoleucinuria (8.2±0.2 mg/mL) (p<0.05); QT elicited methioninuria (23.1±0.3 mg/mL) in T1DM and the control (p<0.001); AAM+QT alleviated the methioninuria with extra leucinuria (11.3±0.4 mg/mL) (p<0.05), isoleucinuria (11.4±0.4 mg/mL), tryptophanuria, argininuria and lysinuria (p<0.05). Conclusion: T1DM exhibits severe insulin insufficiency, resulting in severe body weight loss and increased kidney/body weight ratio. T1DM and QT tend to induce methioninineuria. AAM+QT can rescue methioninuria at the expense of leucinuria, isoleucinuria, tryptophanuria, argininuria and lysinuria, implicating the use of AAM with extra supplement of insulin, leucine, isoleucine, tryptophan, arginine and lysine is feasible for alleviation of T1DM.