Oetjen Elke
Department of Clinical Pharmacology and Toxicology, Pharmacology for Pharmacist's Unit, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
DZHK (German Centre for Cardiovascular Research) Partner Site Hamburg/Kiel/Lübeck, Germany.
Arch Pharm (Weinheim). 2016 Jun;349(6):410-3. doi: 10.1002/ardp.201600053. Epub 2016 Apr 21.
Diabetes mellitus is one of the most rapidly increasing diseases worldwide, whereby approximately 90-95% of patients suffer from type 2 diabetes. Considering its micro- and macrovascular complications like blindness and myocardial infarction, a reliable anti-diabetic treatment is needed. Maintaining the function and the mass of the insulin producing beta-cells despite elevated levels of beta-cell-toxic prediabetic signals represents a desirable mechanism of action of anti-diabetic drugs. The dual leucine zipper kinase (DLK) inhibits the action of two transcription factors within the beta-cell, thereby interfering with insulin secretion and production and the conservation of beta-cell mass. Furthermore, DLK action is regulated by prediabetic signals. Hence, the inhibition of this kinase might protect beta-cells against beta-cell-toxic prediabetic signals and prevent the development of diabetes. DLK might thus present a novel drug target for the treatment of diabetes mellitus type 2.
糖尿病是全球发病率增长最为迅速的疾病之一，约90 - 95%的患者患有2型糖尿病。鉴于其微血管和大血管并发症，如失明和心肌梗死，需要可靠的抗糖尿病治疗方法。尽管处于β细胞毒性糖尿病前期信号水平升高的状态，但维持产生胰岛素的β细胞的功能和数量是抗糖尿病药物理想的作用机制。双亮氨酸拉链激酶（DLK）抑制β细胞内两种转录因子的作用，从而干扰胰岛素分泌和生成以及β细胞数量的维持。此外，DLK的作用受糖尿病前期信号调节。因此，抑制这种激酶可能保护β细胞免受β细胞毒性糖尿病前期信号的影响，并预防糖尿病的发生。DLK可能因此成为治疗2型糖尿病的新型药物靶点。
