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.

Maintaining the function and mass of the insulin‐producing beta‐cells despite elevated levels of beta‐cell‐toxic prediabetic signals is a desirable mechanism of action of anti‐diabetic drugs. The dual leucine zipper kinase, which inhibits the action of two transcription factors within beta‐cells and is regulated by prediabetic signals, might be a novel drug target for the treatment of diabetes mellitus type 2.