Regulation of Beta-Cell Function and Mass by the Dual Leucine Zipper Kinase

Arch Pharm (Weinheim). 2016 Jun;349(6):410-3. doi: 10.1002/ardp.201600053. Epub 2016 Apr 21.

Abstract

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.

Keywords: Beta-cells; Diabetes mellitus; Dual leucine zipper kinase.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Humans
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / enzymology*
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • MAP Kinase Kinase Kinases / metabolism*
  • Molecular Targeted Therapy / methods

Substances

  • MAP Kinase Kinase Kinases
  • MAP3K13 protein, human