Hwang I K, Go V L W, Harris D M, Yip I, Kang K W, Song M K
UCLA Center for Human Nutrition, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Diabetes Obes Metab. 2003 Sep;5(5):317-24. doi: 10.1046/j.1463-1326.2003.00281.x.
The specific objective of this study was to determine acute and long-term effects of cyclo (his-pro) (CHP) plus zinc and l-histidine (CZH) treatment on glucose metabolism in genetically obese (ob/ob), type 2 diabetic mice.
Acute effects of 0.3 mg of CHP plus 10 mg of zinc and 0.5 mg of l-histidine/kg body weight (BW) on fed blood glucose concentrations and 3-h average of above fasting blood glucose concentrations (TAFGCs), an index of oral glucose tolerance test, in lean and ob/ob mice were determined. To evaluate long-term effects of CZH on TAFGCs, lean and ob/ob mice were treated with drinking water containing increasing doses of CHP (0, 0.5, 1.0 or 1.5 mg/l) plus 10 mg zinc and 0.5 mg of l-histidine/l for 3 weeks. During the treatment period, fed blood glucose concentrations, BW and food and water intake were determined. At the end of the treatment, fasting blood glucose concentrations, TAFGC and fed plasma insulin concentrations were determined.
Blood glucose concentrations significantly decreased when CZH was administered acutely via gastric gavage in food-deprived ob/ob mice. Similarly, 1.0 mg/l CHP treatment of mice with fixed amounts of 10 mg zinc and 0.5 mg l-histidine/l was optimal to decrease fed blood glucose and plasma insulin concentrations during a 3-week treatment period in ob/ob mice. TAFGC values in these mice also improved most significantly with the same combination of CHP, zinc and l-histidine used to test for fed blood glucose and plasma insulin levels. Fasting blood glucose concentrations and BW gains also decreased in ob/ob mice treated with 1.0 mg of CHP/l plus the same amount of zinc and l-histidine used in the above experiments. No effects of CZH treatment in lean mice were observed.
CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti-hyperglycaemic agent.
本研究的具体目标是确定环（组氨酸-脯氨酸）（CHP）加锌和L-组氨酸（CZH）治疗对遗传性肥胖（ob/ob）2型糖尿病小鼠葡萄糖代谢的急性和长期影响。
测定0.3毫克CHP加10毫克锌和0.5毫克L-组氨酸/千克体重（BW）对正常小鼠和ob/ob小鼠进食时血糖浓度以及上述空腹血糖浓度3小时平均值（TAFGCs，口服葡萄糖耐量试验指标）的急性影响。为评估CZH对TAFGCs的长期影响，正常小鼠和ob/ob小鼠饮用含递增剂量CHP（0、0.5、1.0或1.5毫克/升）加10毫克锌和0.5毫克L-组氨酸/升的水，持续3周。在治疗期间，测定进食时血糖浓度、BW以及食物和水的摄入量。治疗结束时，测定空腹血糖浓度、TAFGC和进食时血浆胰岛素浓度。
在饥饿的ob/ob小鼠中通过灌胃急性给予CZH时，血糖浓度显著降低。同样，在ob/ob小鼠为期3周的治疗期间，用固定量的10毫克锌和0.5毫克L-组氨酸/升加1.0毫克/升CHP治疗，最有利于降低进食时血糖和血浆胰岛素浓度。用相同组合的CHP、锌和L-组氨酸来检测进食时血糖和血浆胰岛素水平时，这些小鼠的TAFGC值也改善最为显著。用1.0毫克/升CHP加上述实验中相同量的锌和L-组氨酸治疗的ob/ob小鼠，空腹血糖浓度和体重增加也有所降低。未观察到CZH治疗对正常小鼠有影响。
CZH可有效降低遗传性肥胖（ob/ob）2型糖尿病小鼠的血糖浓度。这些数据支持我们的工作假设，即CZH可能是一种重要的抗高血糖药物。
