The Network of Glucokinase-Expressing Cells in Glucose Homeostasis and the Potential of Glucokinase Activators for Diabetes Therapy
Authors
Discussion
Loading...
Member takes
Implication
Mechanistic review demonstrates the central glucose-sensing role of glucokinase in neuroendocrine and hepatic cells, highlighting allosteric activators as promising antidiabetic therapies.
Key Points
- To review the role of glucokinase as the body's primary glucose sensor and assess the therapeutic potential of allosteric glucokinase activators for diabetes.
- Synthesized molecular, kinetic, and structural evidence on glucokinase in pancreatic beta-cells and hepatocytes.
- Evaluated human clinical data on activating and inactivating glucokinase mutations that cause hypo- and hyperglycemia syndromes.
- Assessed pharmacological mechanisms of glucokinase activators modulating allosteric enzyme activity.
- Pancreatic beta-cells act as the prototype master glucose sensor, while liver parenchymal cells harbor 99% of glucokinase to drive high-capacity blood glucose clearance.
- Genetic variations in glucokinase cause distinct hypo- and hyperglycemic disorders in humans, validating the glucose sensor paradigm.
- Allosteric glucokinase activators increase kcat and lower the glucose S(0.5), stimulating islet insulin secretion and enhancing liver glucose disposition.
Cite This Study
Matschinsky et al. (2006) studied this question.