Glucokinase - Distribution Among Organ Systems

Distribution Among Organ Systems

Glucokinase has been discovered in specific cells in four types of mammalian tissue: liver, pancreas, small intestine, and brain. All play crucial roles in responding to rising or falling levels of blood glucose.

• The predominant cells of the liver are the hepatocytes, and GK is found exclusively in these cells. During digestion of a carbohydrate meal, when blood glucose is plentiful and insulin levels are high, hepatocytes remove glucose from the blood and store it as glycogen. After completion of digestion and absorption, the liver manufactures glucose from both non-glucose substrates (gluconeogenesis) and glycogen (glycogenolysis), and exports it into the blood, to maintain adequate blood glucose levels during fasting. Because GK activity rises rapidly as the glucose concentration rises, it serves as a central metabolic switch to shift hepatic carbohydrate metabolism between fed and fasting states. Phosphorylation of glucose to glucose-6-phosphate by GK facilitates storage of glucose as glycogen and disposal by glycolysis. The separate liver promoter allows glucokinase to be regulated differently in hepatocytes than in the neuroendocrine cells.
• Neuroendocrine cells of the pancreas, gut, and brain share some common aspects of glucokinase production, regulation, and function. These tissues are collectively referred to as "neuroendocrine" cells in this context.
  • Beta cells and alpha cells of the pancreatic islets
    • Beta cells release insulin in response to rising levels of glucose. Insulin enables many types of cells to import and use glucose, and signals the liver to synthesize glycogen. Alpha cells produce less glucagon in response to rising glucose levels, and more glucagon if blood glucose is low. Glucagon serves as a signal to the liver to break down glycogen and release glucose into the blood. Glucokinase in beta cells serves as a glucose sensor, amplifying insulin secretion as blood glucose rises.
  • Glucose-sensitive neurons of the hypothalamus
    • In response to rising or falling levels of glucose, cells in the hypothalamus polarize or depolarize. Among the neuroendocrine reactions of the central nervous system to hypoglycemia is activation of the adrenergic responses of the autonomic nervous system. Glucokinase likely serves as a glucose signal here as well. Glucokinase has also been found in cells of the anterior pituitary.
  • Enterocytes of the small intestine
    • This is the least-understood of the glucokinase sensor systems. It seems likely that responses to incoming glucose during digestion play a role in the incretin amplification of insulin secretion during a meal, or in the generation of satiety signals from gut to brain.