Glucokinase: old enzyme, new target

Abstract

Glucokinase (GK) plays a key role as a glucose sensor in pancreatic β-cells and in the regulation of glucose utilisation in hepatocytes. Defects in the GK gene have been linked to maturity-onset diabetes of the young (non-insulin-dependent [MODY-2]), permanent neonatal diabetes (PNDM) and persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI). Expression of GK is regulated by the upstream pancreatic promoter or the downstream hepatocyte promoter by a scenario involving several transcription factors and signalling pathways that are not yet understood in full. Thus, the development of specific drugs that enhance either GK activity or GK expression could be useful for treatment of the diabetic syndromes. Due to a recent breakthrough leading to the identification of a novel class of small molecules termed glucokinase activators, the old enzyme became a new target in diabetes therapy.

Keywords::

• β-cell
• glucokinase
• glucokinase activator
• hepatocyte
• insulin
• MODY-2
• pancreas