uridine + glucose

Uridine + glucose is a combination of the nucleoside uridine and the monosaccharide glucose that serves as a metabolic precursor for the biosynthesis of uridine diphosphate glucose (UDP-glucose). Recent research has identified UDP-glucose as an endogenous molecular glue that facilitates the recruitment of glucokinase (GCK) to the cereblon (CRBN) E3 ubiquitin ligase complex. This recruitment triggers the ubiquitination and subsequent proteasomal degradation of glucokinase, a key enzyme in glucose sensing and insulin secretion. In pancreatic β-cells, this degradation leads to reduced glucose-6-phosphate production and a decrease in glucose-induced insulin secretion. This mechanism suggests that UDP-glucose acts as a metabolic signal to regulate glucose homeostasis, and its dysregulation may play a role in the pathogenesis of Maturity-onset diabetes of the young type 2 (MODY2), where certain GCK mutations exhibit resistance to this degradation pathway. The combination is primarily studied in the context of metabolic regulation and targeted protein degradation (TPD).