Regulation of Beta-Cell Function and Mass by the Dual Leucine Zipper Kinase.
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.
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.|Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
Elke
E
Oetjen
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000201:enzymology*; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods
D020930:MAP Kinase Kinase Kinases; C109162:MAP3K13 protein, human
Beta-cells; Diabetes mellitus; Dual leucine zipper kinase