Local microvascular regulatory mechanisms in diabetes: relevance to neuropathy

在糖尿病中，血液中过多的糖分可能会引起细胞内代谢过程的变化，从而导致循环系统和神经系统的功能紊乱。这种紊乱已被证明发生在糖尿病的早期阶段，并最终导致长期后果，包括伤口愈合不良(通常最终导致肢体截肢)、失明风险增加、肾脏疾病和心力衰竭。目前还不可能恢复正常的新陈代谢，使患者面临发生涉及循环系统和神经系统的并发症的风险。了解这些并发症的发展过程将有助于制定替代治疗策略，以改善糖尿病患者的生活质量和预期寿命。导致循环系统和神经系统功能异常的事件尚不确定，然而，研究表明，糖尿病患者可能存在神经血液供应不足，这可能会导致神经损伤。目前，我们对神经血流调节因素的了解还很有限。这项建议中描述的研究旨在检验这样一种假设，即神经血管本身通过一种内在的能力参与流量的调节，这种能力可以根据组织需求改变其直径，并且在糖尿病中，神经血管收缩或扩张能力的改变会损害它们在控制神经血流量方面的作用。从这些研究中获得的信息将提高我们对早期循环系统和神经系统功能障碍的理解，这些障碍导致血液流动的变化，这些变化发生在糖尿病相关并发症的明显变化之前。这将为开发糖尿病患者的新治疗策略提供洞察力。

In diabetes mellitus, the excessive levels of sugar in the blood may cause changes in metabolic processes within cells that lead to disturbances in the function of the circulatory and nervous systems. Such disturbances have been shown to occur in the early stages of diabetes and ultimately lead to longterm consequences including poor wound healing (often culminating in limb amputations), increased risk of blindness, kidney disease and heart failure. At present it is not possible to restore normal metabolism, leaving patients at risk of developing complications involving the circulatory and nervous systems. An understanding of the processes involved in the development of such complications would allow alternate treatment strategies to be devised in order to improve the quality of life and life expectancy of diabetic patients. The events leading to abnormalities in the function of the circulatory and nervous systems are uncertain, however, studies have demonstrated that in diabetes there may be an insufficient blood supply to nerves and this would be expected to cause nerve damage. At present, our understanding of the factors involved in regulating blood flow to nerves is limited. The studies described in this proposal are aimed at testing the hypothesis that nerve blood vessels are themselves involved in the regulation of flow through an intrinsic ability to change their diameter in response to tissue demands and that in diabetes alterations in the capacity of nerve blood vessels to constrict or dilate compromises their role in the control of nerve blood flow . Information obtained from these studies will improve our understanding of the early disturbances in the function of circulatory and nervous systems leading to alterations in blood flow which precede the development of overt changes characteristic of the complications associated with diabetes. This will provide insight into developing new treatment strategies for diabetic patients.