Glycolysis in the control of blood glucose homeostasis

Glycolysis, a simple pathway of glucose metabolism, critically regulates insulin secretion and metabolic functions of various cells. Depending on cell types, rates of glycolysis are determined at various steps of glycolysis that are subjected to the control of key metabolic and regulatory enzyme(s), which include glucokinase, 6-phosphofructo-1-kinase, and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. These enzymes are regulated by both nutritional and hormonal signals at the levels of transcription, translation, and post-translational modifications. In hepatocytes, glycolysis is involved in the control of hepatic glucose production. The latter, when excessive, contributes to hyperglycemia in diabetes. In pancreatic β cells, glycolysis couples glucose-stimulated insulin secretion. Absolute or relatively low levels of circulating insulin causes hyperglycemia. In adipocytes, glycolysis generates metabolites for lipogenesis and channels fatty acids from excessive oxidation to triglyceride synthesis, thereby reducing oxidative stress. With increased proinflammatory status, adipocytes produce pro-hyperglycemic factors and bring about hyperglycemia and insulin resistance. In hypothalamic neurons, glycolysis conveys nutrient sensing that is related to feeding control. Dysregulation of glycolysis occurs in conditions of insulin deficiency or resistance, and is attributable to inappropriate amount and/or activities of metabolic and regulatory enzymes of glycolysis. Targeting key metabolic and regulatory enzymes to enhance glycolysis may offer viable approaches for treatment of diabetes.