DPP-4抑制剂对胰岛β-细胞和α-细胞功能的影响

发布时间：2018-06-05 23:42

本文选题：二肽基肽酶-4抑制剂 + β-细胞　；参考：《重庆医科大学》2015年硕士论文

【摘要】：第一部分：DPP-4抑制剂对胰岛β-细胞功能的影响糖尿病发生发展的根本原因在于胰岛功能的进行性衰竭,其中既包括胰岛β-细胞分泌胰岛素(INS)缺陷,同时也存在α-细胞不适当的分泌胰高血糖素以及外周组织存在的胰岛素抵抗作用。如何改善糖尿病患者的胰岛功能,进而延缓疾病进展已成为目前糖尿病治疗的新热点。二肽基肽酶-4(DPP-4)抑制剂(DPP-4I)是近年来一种新型降血糖药物,在各种糖尿病(DM)动物模型中可见DPP-4I能增加β-细胞团,修复损伤的胰岛细胞分布,增加胰岛素量。而临床研究中,研究者们虽选用的评价手段各不同,剂量及疗程长短不一,但无论在空腹或糖负荷下都观察到DPP-4I治疗后可增加患者胰岛素分泌、减轻胰岛素抵抗等从而改善β-细胞功能。目前,大多数临床研究表明DPP-4I降低血糖的疗效值得肯定,其对胰岛β-细胞功能的改善是显著的；其疗效甚至不受胰岛素抵抗程度、BMI、病程长短的影响。第二部分：DPP-4抑制剂对胰岛α-细胞功能的影响正常人体内,胰岛素与胰高血糖素共同参与并维持血糖稳态,存在血糖调节紊乱的糖尿病患者中,不仅存在β-细胞功能异常,同时存在α-细胞功能受损,胰高血糖素分泌紊乱。“双激素”理论更加全面的体现了糖尿病的发生发展机制。在多数糖尿病患者中,研究者观察到胰高血糖素水平异常增高,其机制仍不十分明了,目前发现可能与a-细胞对葡萄糖的反应性降低、胰岛素对胰高血糖素的抑制作用减弱、肠促胰素的调节作用异常、α-细胞的胰岛素抵抗、胰高血糖素对β-细胞的促分泌作用、神经系统调节受损、α-细胞原发功能障碍等因素有关。二肽基肽酶-4抑制剂(DPP-4I)作为近年来一种新型降血糖药物,许多研究者在糖尿病动物模型中观察到其可作用于α-细胞,修复细胞的分布紊乱,同时降低胰高血糖素水平。临床研究中,无论是短期或长期应用DPP-4I都能有效的降低2型糖尿病患者胰高血糖素水平,改善α-细胞分泌紊乱,从而更好的控制血糖水平。在糖耐量受损、1型糖尿病以及类固醇性糖尿病患者中,此作用亦存在。
[Abstract]:The first part: the effect of 1: DPP-4 inhibitor on the function of islet 尾-cells. The fundamental cause of the development of diabetes is the progressive failure of islet function, which includes the deficiency of insulin secretion by islet 尾-cells. At the same time, there is also an inappropriate secretion of glucagon by 伪-cells and insulin resistance in peripheral tissues. How to improve the islet function of diabetic patients and delay the progress of diabetes has become a new focus of diabetes treatment. Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new type of hypoglycemic drug in recent years. DPP-4I can increase 尾 -cell mass, repair the distribution of damaged islet cells and increase the amount of insulin in various animal models of diabetes mellitus (DM). In clinical studies, although the different evaluation methods, dose and duration of treatment were different, the researchers observed that the insulin secretion was increased after DPP-4I treatment on an empty stomach or under glucose load. To reduce insulin resistance and improve the function of 尾-cells. At present, most clinical studies show that the effect of DPP-4I on reducing blood glucose is worthy of recognition, and the improvement of islet 尾-cell function is significant, and the effect is not even affected by the degree of insulin resistance and the duration of the disease. The second part: the effect of DPP-4 inhibitor on the function of islet 伪-cells in normal human body, insulin and glucagon participate in and maintain blood glucose homeostasis together, and there is not only 尾-cell dysfunction in diabetic patients with impaired blood glucose regulation. At the same time, 伪-cell function was impaired and glucagon secretion was disturbed. The "double hormone" theory reflects the development mechanism of diabetes more comprehensively. In most patients with diabetes, researchers have observed an abnormal increase in glucagon levels, the mechanism of which is still unclear, and it has been found that there may be a decrease in the responsiveness of a-cell to glucose and a decrease in the inhibitory effect of insulin on glucagon The regulation of glucagon is abnormal, the insulin resistance of 伪 -cell, the effect of glucagon on 尾 -cell secretion, the damage of nervous system regulation, the primary dysfunction of 伪 -cell, and so on. Dipeptidyl peptidase-4 inhibitor (DPP-4I) is a new hypoglycemic drug in recent years. Many researchers have observed that DPP-4I can act on 伪-cells in diabetic animal models, repair the disorder of cell distribution, and decrease the level of glucagon at the same time. In clinical research, whether short-term or long-term application of DPP-4I can effectively reduce the level of glucagon in patients with type 2 diabetes, improve the disorder of 伪 -cell secretion, and control the level of blood sugar better. This effect is also present in patients with impaired glucose tolerance and type 1 diabetes and steroid diabetes.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R587.1

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