Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States of America.
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, United States of America.
J Control Release. 2021 Apr 10;332:21-28. doi: 10.1016/j.jconrel.2021.02.013. Epub 2021 Feb 16.
Diabetes is a chronic disease involving elevated blood glucose levels. Controlled insulin delivery is an ideal method to achieve glycemic control. However, glucose levels vary as a result of changes in the body's physiological conditions resulting from different daily events, such as meals, exercise and stress. It is essential to develop and to monitor appropriate biomarkers for these natural physiological perturbations in order to achieve a holistic understanding of metabolic changes in diabetic patients to facilitate optimal glucose management and make possible personalized medicine for this very debilitating disease. The novel aspects of the current research include the combination of the tail suspension stress animal model and microdialysis for stress biomarker monitoring. A tail suspension test was optimized and used as a stress inducer for different groups of model rats (normal, untreated diabetic and insulin-treated diabetic rats). The levels of multiple metabolic analytes in the subcutaneous tissue were monitored continuously using subcutaneous microdialysis analysis. Different analytes, including pH, glucose and lactate were monitored and analyzed. Another important and original aspect of the reported work is that revelation that the pH, lactate and glucose levels increased under the stress conditions and the changes tended to be more pronounced in diabetic rats (both untreated and long-acting insulin-treated) compared to normal rats. Long-acting insulin treatment was shown to shorten the duration of the pH and glucose changes in response to stress when compared to the untreated diabetic rats. An additional novel aspect of the research is that subcutaneous pH was shown to be a sensitive stress biomarker for diabetic rats as pH changes rapidly after stress initiation. This research provides insight into the importance of accurate glycemic control and diabetes management for individual patients through highlighting stress management and appropriate biomarker monitoring, especially the value of combining pH and lactate monitoring with typical glucose monitoring. This research will pave the way for individualized medicine for diabetic patients through helping to obtain a holistic understanding of the various important biomarkers, rather than solely depending on glucose monitoring to determine appropriate insulin dosing.
糖尿病是一种涉及血糖升高的慢性疾病。控制胰岛素的输送是实现血糖控制的理想方法。然而，由于不同日常事件（如进餐、运动和应激）引起的身体生理条件的变化，血糖水平会发生变化。为了全面了解糖尿病患者的代谢变化，以促进最佳血糖管理并为这种非常衰弱的疾病实现个性化医疗，开发和监测适当的生物标志物来监测这些自然生理波动至关重要。当前研究的新颖之处在于将尾部悬吊应激动物模型和微透析技术结合起来，用于应激生物标志物监测。对尾部悬吊试验进行了优化，并将其用作不同模型大鼠组（正常、未治疗的糖尿病和胰岛素治疗的糖尿病大鼠）的应激诱导剂。使用皮下微透析分析连续监测皮下组织中多种代谢分析物的水平。监测和分析了不同的分析物，包括 pH 值、葡萄糖和乳酸。所报道工作的另一个重要和原创方面是，揭示了在应激条件下 pH 值、乳酸和葡萄糖水平升高，与正常大鼠相比，未治疗和长效胰岛素治疗的糖尿病大鼠的变化更为明显。与未治疗的糖尿病大鼠相比，长效胰岛素治疗显示可缩短 pH 值和葡萄糖对应激的变化持续时间。研究的另一个新颖方面是，皮下 pH 值被证明是糖尿病大鼠的敏感应激生物标志物，因为 pH 值在应激开始后迅速变化。这项研究通过强调应激管理和适当的生物标志物监测，特别是将 pH 值和乳酸监测与典型的葡萄糖监测相结合的价值，为个体化医疗提供了思路，从而为糖尿病患者提供了个性化医疗。这将有助于全面了解各种重要的生物标志物，而不仅仅依赖于葡萄糖监测来确定适当的胰岛素剂量，从而为糖尿病患者的个体化医疗铺平道路。
