Wientjes K J, Vonk P, Vonk-van Klei Y, Schoonen A J, Kossen N W
Department of Pharmaceutical Technology and Biopharmacy, University Center of Pharmacy, University of Groningen, The Netherlands.
Diabetes Care. 1998 Sep;21(9):1481-8. doi: 10.2337/diacare.21.9.1481.
To measure possible changes in dialysate glucose concentrations over time, to validate the diffusional model for glucose transport from tissue to the probe, and to evaluate the actual glucose concentration in adipose tissue.
Glucose concentrations in the subcutaneous adipose tissue of five healthy subjects (age 25 +/- 2.7 years, BMI 23.2 +/- 2.3 kg/m2 [mean +/- SD]) were measured by the microdialysis technique and compared with blood glucose. We applied microdialysis probes with hollow fibers of various membrane length (10-35 mm), used eight perfusion flow rates (0.5-20 microl/min), and perfused four glucose solutions (0.0, 2.8, 8.3, 11.1 mmol/l).
After implantation, a substantial decrease in glucose recovery to the lowest value of 26 +/- 10% of the final plateau value was noted during the first few hours (n = 4). Recovery increased and stabilized after 5-9 days at 84.0 +/- 7.4% of capillary blood glucose when a flow rate of 0.5 microl/min was applied. According to the zero net-flux method, the glucose concentration in equilibrium, Cequi, with the surrounding tissue can be obtained. This concentration also decreases; however, 1 h after recovery, Cequi increases again over 1 or 2 days to a stable value that is not significantly different from the measured capillary blood glucose (P < 0.05). Using various perfusion flow rates and probes (membrane length 10-35 mm), it is shown that diffusion is the rate-limiting process for glucose transport through tissue.
Insertion of the microdialysis probes causes damage to the adipose cells and the vascular bed around the probe. Glucose recovery decreases because of a lower blood supply. In 5-9 days, glucose recovery increases; apparently, this time is needed to repair the microstructure of tissue around the probe. After stabilization of the recovery, no loss of probe permeability, which is due to biocompatibility problems, was seen. The change during the 2 days in equilibrium concentration is probably caused by an inflammation reaction that consumes glucose around the probe. The individual increase in recovery during the 1st days after probe insertion until a stable plateau value is reached (flow rate >0 microl/min) is complicated for short-term clinical glucose measurements in adipose tissue. After stabilization, the mean equilibrium concentration of all subjects was equal to the mean capillary blood glucose concentration. Therefore, we conclude that capillary blood glucose concentration probably is the driving force for diffusion through the capillary wall into the probe and is not some interstitial concentration.
测量透析液葡萄糖浓度随时间的可能变化，验证葡萄糖从组织向探针转运的扩散模型，并评估脂肪组织中的实际葡萄糖浓度。
采用微透析技术测量了5名健康受试者（年龄25±2.7岁，体重指数23.2±2.3kg/m²[平均值±标准差]）皮下脂肪组织中的葡萄糖浓度，并与血糖进行比较。我们应用了具有不同膜长度（10 - 35mm）中空纤维的微透析探针，使用了8种灌注流速（0.5 - 20μl/min），并灌注了4种葡萄糖溶液（0.0、2.8、8.3、11.1mmol/l）。
植入后，在最初几小时内观察到葡萄糖回收率大幅下降至最终平台值的最低值26±10%（n = 4）。当应用0.5μl/min的流速时，5 - 9天后回收率增加并稳定在毛细血管血糖的84.0±7.4%。根据零净通量法，可以获得与周围组织平衡时的葡萄糖浓度Cequi。该浓度也会降低；然而，回收率1小时后，Cequi在1或2天内再次增加至稳定值，与测量的毛细血管血糖无显著差异（P < 0.05）。使用不同的灌注流速和探针（膜长度10 - 35mm）表明，扩散是葡萄糖通过组织转运的限速过程。
微透析探针的插入会对探针周围的脂肪细胞和血管床造成损伤。由于血液供应减少，葡萄糖回收率降低。在5 - 9天内，葡萄糖回收率增加；显然，需要这段时间来修复探针周围组织的微观结构。回收率稳定后，未观察到由于生物相容性问题导致的探针通透性丧失。平衡浓度在2天内的变化可能是由探针周围消耗葡萄糖的炎症反应引起的。在探针插入后的第1天内，回收率个体增加直至达到稳定的平台值（流速>0μl/min），这对于脂肪组织中短期临床葡萄糖测量来说较为复杂。稳定后，所有受试者的平均平衡浓度等于平均毛细血管血糖浓度。因此，我们得出结论，毛细血管血糖浓度可能是葡萄糖通过毛细血管壁扩散进入探针的驱动力，而不是某些间质浓度。
