Wi J K, Kim J K, Youn J H
Department of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles 90033, USA.
Am J Physiol. 1998 Feb;274(2):E257-64. doi: 10.1152/ajpendo.1998.274.2.E257.
The relationships between postabsorptive glucose concentration and hepatic glucose output (HGO) and glucose clearance were studied in rats one day after treatment with various doses of streptozotocin (STZ; 0, 15, 30, 40, 50, or 75 mg/kg; n = 6 per dose; study 1). Glucose fluxes were estimated using a prolonged (6-h) infusion of [3-3H]glucose to ensure complete tracer equilibration at hyperglycemia. Postabsorptive glucose was significantly increased at the high doses of STZ (50 and 75 mg/kg; P < 0.01) and was strongly correlated with glucose clearance across all doses (r = -0.85, P < 0.001) but less strongly with HGO (r = 0.46, P < 0.01). In the group treated with 50 mg/kg STZ, postabsorptive glucose was increased twofold compared with the control (i.e., zero dose) group, with no change in HGO and a 45% decrease in glucose clearance, indicating that the hyperglycemia was due to a decrease in glucose clearance. To understand the cellular mechanisms of decreased glucose clearance in STZ diabetic rats, skeletal muscle glucose clearance and intracellular glucose and glucose 6-phosphate (G-6-P) concentrations were determined in normal and STZ (50 mg/kg) diabetic rats at their postabsorptive glucose levels as well as at matched hyperglycemia (12 mM; study 2). Glucose clearance was significantly decreased in soleus (P < 0.05) muscles of the diabetic rats, and this was associated with significantly decreased intracellular glucose and G-6-P levels at matched hyperglycemia (P < 0.05), suggestive of decreased glucose transport. In conclusion, postabsorptive hyperglycemia in STZ diabetic rats was largely due to decreased glucose clearance, although increased HGO may also have been a contributing factor at the highest STZ dose. The decrease in postabsorptive glucose clearance in STZ diabetic rats appeared to be associated with an impairment of glucose transport in soleus (type I) muscles.
在使用不同剂量链脲佐菌素（STZ；0、15、30、40、50或75mg/kg；每组n = 6；研究1）治疗大鼠一天后，研究了空腹血糖浓度与肝葡萄糖输出（HGO）及葡萄糖清除率之间的关系。使用[3-3H]葡萄糖进行长时间（6小时）输注来估计葡萄糖通量，以确保在高血糖状态下示踪剂完全平衡。高剂量STZ（50和75mg/kg）时空腹血糖显著升高（P < 0.01），且在所有剂量下与葡萄糖清除率均呈强相关（r = -0.85，P < 0.001），但与HGO的相关性较弱（r = 0.46，P < 0.01）。在接受50mg/kg STZ治疗的组中，空腹血糖相比对照组（即零剂量组）增加了两倍，HGO无变化，葡萄糖清除率降低了45%，这表明高血糖是由于葡萄糖清除率降低所致。为了解STZ糖尿病大鼠葡萄糖清除率降低的细胞机制，在正常和STZ（50mg/kg）糖尿病大鼠的空腹血糖水平以及匹配的高血糖状态（12mM；研究2）下，测定了骨骼肌葡萄糖清除率以及细胞内葡萄糖和葡萄糖6-磷酸（G-6-P）浓度。糖尿病大鼠比目鱼肌的葡萄糖清除率显著降低（P < 0.05），且在匹配的高血糖状态下细胞内葡萄糖和G-6-P水平显著降低（P < 0.05），提示葡萄糖转运减少。总之，STZ糖尿病大鼠的空腹高血糖主要是由于葡萄糖清除率降低，尽管在最高STZ剂量时HGO增加也可能是一个促成因素。STZ糖尿病大鼠空腹葡萄糖清除率的降低似乎与比目鱼肌（I型）中葡萄糖转运受损有关。
