1. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, 250 Wu-Xing St., 110, Taipei, Taiwan.
2. Department of Applied Food Technology, Hungkuang University, 34 Chung-Chie Rd., Shalu District, Taichung City, 43302, Taiwan.
3. Graduate Institute of Biotechnology, Changhua University of Education, 1 Jin-De Rd., Changhua, Taiwan.
4. Department of Internal Medicine, Chung-Shan Medical University, 110 Sec.-1, Chien-Kuo North Road, Nan-Toon District, Taichung City 402, Taiwan.
5. Division of Endocrinology and Metabolism, Chung-Shan Medical University Hospital, 110 Sec.-1, Chien-Kuo North Road, Nan-Toon District, Taichung City 402, Taiwan.
7. Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, 250, Wu-Xin St., Xin-Yi District, 110, Taipei, Taiwan.
8. Research Institute of Biotechnology, Hungkuang University, 34 Chung-Chie Rd., Shalu District, Taichung City, 43302, Taiwan.
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.
Keywords: Type 1DM, methioninuria, serinuria, leucinuria, amino acid therapy