Glucokinase as glucose sensor and metabolic signal generator in pancreatic beta-cells and hepatocytes.
This article reviews evidence for a pivotal role of glucokinase as glucose sensor of the pancreatic beta-cells. Glucokinase explains the capacity, hexose specificity, affinities, sigmoidicity, and anomeric preference of pancreatic islet glycolysis, and because stimulation of glucose metabolism is a prerequisite of glucose stimulation of insulin release, glucokinase also explains many characteristics of this beta-cell function. Glucokinase of the beta-cell is induced or activated by glucose in contrast to liver glucokinase, which is regulated by insulin. Tissue-specific regulation corresponds with observations that liver and pancreatic beta-cell glucokinase are structurally distinct. Glucokinase could play a glucose-sensor role in hepatocytes as well, and certain forms of diabetes mellitus might be due to glucokinase deficiencies in pancreatic beta-cells, hepatocytes, or both.
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia 19104-6015.
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FM
Matschinsky
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005941:Glucokinase / Q000032:analysis*; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009747:Nutritional Physiological Phenomena / Q000502:physiology; D015398:Signal Transduction
D001786:Blood Glucose; D005941:Glucokinase