The accumulation of HIF-1α induced by hyperglycemia increases LDHA activity and HK2, PFKP expression, thereby promoting pancreatic glycolysis to facilitate cancer progression.
Hexokinase-2 (HK2) was recently found to produce increased metabolic flux through glycolysis in hyperglycemia without concurrent transcriptional or other functional regulation.
However, glucose phosphorylation can represent a rate-limiting step for skeletal muscle glucose utilization since muscle glucose-6-phosphate levels are increased during in vivo hyperinsulinemia and hyperglycemia; furthermore, basal and insulin-mediated muscle glucose uptake can be increased by a selective increase in HKII expression.