摘要
二型糖尿病(T2D)的发病率在全球范围内急剧增加,且已经造成了巨大的医疗负担。肥胖症,血脂异常和胰岛素耐受性是T2D发展的主要风险因素,但是导致这种疾病的主要因素是胰岛素β细胞群的生成来补偿身体里面胰岛素需求不断增加的失败。疾病的发展机一部减少了β细胞群,从而导致对β细胞特别敏感的脂毒性和糖毒性。因此,治疗旨在预防β细胞减少或增加β细胞的数量可能抑制糖尿病的进程或者导致正常新陈代谢的恢复。然而,现在的和新的抗糖尿病药物主要将胰岛素分泌和活动或者葡萄糖摄取作为靶标,必须找到更新的干预措施来组织β细胞的损失或增加β细胞数量。这种靶点是β细胞增殖,新生和存活。本文研究了主要的动物实验数据,这些数据表明通过活性化合物例如生长因子,细胞因子,荷尔蒙,天然化合物和小分子用来调节β细胞群是可行的。通常,由于用来评估化合物在β细胞动力学的作用的方法不足,因此它的作用方式仍然不清楚。此外,一个主要挑战是通过充分的特异性来鉴别化合物以避免一些其他细胞类型的副作用。如果所提出的这样的安全问题能够被解决,这就可能为糖尿病的治疗提供了一个治疗方法。
关键词: β细胞,糖尿病,胰岛素,胰岛,胰腺,再生医学
Current Drug Targets
Title:Regulating the Beta Cell Mass as a Strategy for Type-2 Diabetes Treatment
Volume: 16 Issue: 5
Author(s): Imane Song, Christo Muller, Johan Louw and Luc Bouwens
Affiliation:
关键词: β细胞,糖尿病,胰岛素,胰岛,胰腺,再生医学
摘要: The incidence of type 2 diabetes (T2D) increases dramatically worldwide and has created an enormous health care burden. Obesity, dyslipidemia and insulin resistance are major risk factors for the development of T2D, but the major factor leading to the disease is failure of the insulin-producing beta cell mass to compensate for increasing insulin demands of the body. Progression of the disease further diminishes the beta cell mass as a result of lipotoxicity and glucotoxicity for which beta cells are particularly sensitive. Hence, treatment aiming to prevent beta cell loss or increase the number of beta cells could inhibit diabetes progression or lead to restoration of normal metabolism. Whereas current and new antidiabetic drugs are mainly targeting insulin secretion and action or glucose uptake, newer interventions must be found that prevent beta cell loss or increase beta cell number. The targets for this are beta cell proliferation, neogenesis and survival. This review examines major evidence from animal experiments suggesting that it is feasible to regulate the beta cell mass by bioactive compounds like growth factors, cytokines, hormones, phytochemicals and small molecules. Often the mode of action remains unclear due to inadequate methods to assess the effects of the compounds on the beta cell dynamics. Furthermore, a major challenge is to identify compounds with sufficient specificity in order to avoid unwanted effects on other cell types. Provided such safety issues can be solved, this may provide a curative approach for diabetes treatment.
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Imane Song, Christo Muller, Johan Louw and Luc Bouwens , Regulating the Beta Cell Mass as a Strategy for Type-2 Diabetes Treatment, Current Drug Targets 2015; 16 (5) . https://dx.doi.org/10.2174/1389450116666150204113928
DOI https://dx.doi.org/10.2174/1389450116666150204113928 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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