Rapid translocation of hepatic glucokinase in response to intraduodenal glucose infusion and changes in plasma glucose and insulin in conscious rats
Open Access
- 1 April 2004
- journal article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 286 (4) , G627-G634
- https://doi.org/10.1152/ajpgi.00218.2003
Abstract
The rate of liver glucokinase (GK) translocation from the nucleus to the cytoplasm in response to intraduodenal glucose infusion and the effect of physiological rises of plasma glucose and/or insulin on GK translocation were examined in 6-h-fasted conscious rats. Intraduodenal glucose infusion (28 mg·kg-1·min-1after a priming dose at 500 mg/kg) elevated blood glucose levels (mg/dl) in the artery and portal vein from 90 ± 3 and 87 ± 3 to 154 ± 4 and 185 ± 4, respectively, at 10 min. At 120 min, the levels had decreased to 133 ± 6 and 156 ± 5, respectively. Plasma insulin levels (ng/ml) in the artery and the portal vein rose from 0.7 ± 0.1 and 1.8 ± 0.3 to 11.8 ± 1.5 and 20.2 ± 2.0 at 10 min, respectively, and 12.4 ± 3.1 and 18.0 ± 4.8 at 30 min, respectively. GK was rapidly exported from the nucleus as determined by measuring the ratio of the nuclear to the cytoplasmic immunofluorescence (N/C) of GK (2.9 ± 0.3 at 0 min to 1.7 ± 0.2 at 10 min, 1.5 ± 0.1 at 20 min, 1.3 ± 0.1 at 30 min, and 1.3 ± 0.1 at 120 min). When plasma glucose (arterial; mg/dl) and insulin (arterial; ng/ml) levels were clamped for 30 min at 93 ± 7 and 0.7 ± 0.1, 81 ± 5 and 8.9 ± 1.3, 175 ± 5 and 0.7 ± 0.1, or 162 ± 5 and 9.2 ± 1.5, the N/C of GK was 3.0 ± 0.5, 1.8 ± 0.1, 1.5 ± 0.1, and 1.2 ± 0.1, respectively. The N/C of GK regulatory protein (GKRP) did not change in response to the intraduodenal glucose infusion or the rise in plasma glucose and/or insulin levels. The results suggest that GK but not GKRP translocates rapidly in a manner that corresponds with changes in the hepatic glucose balance in response to glucose ingestion in vivo. Additionally, the translocation of GK is induced by the postprandial rise in plasma glucose and insulin.Keywords
This publication has 41 references indexed in Scilit:
- Glucokinase and glucokinase regulatory protein: mutual dependence for nuclear localizationBiochemical Journal, 2000
- Investigation of the mechanism by which glucose analogues cause translocation of glucokinase in hepatocytes: evidence for two glucose binding sitesBiochemical Journal, 2000
- Mice mutant for glucokinase regulatory protein exhibit decreased liver glucokinase: A sequestration mechanism in metabolic regulationProceedings of the National Academy of Sciences, 1999
- Glucokinase regulatory protein is essential for the proper subcellular localisation of liver glucokinaseFEBS Letters, 1999
- Glucokinase Regulatory Protein May Interact With Glucokinase in the Hepatocyte NucleusDiabetes, 1997
- Glucosamine-Induced Inhibition of Liver Glucokinase Impairs the Ability of Hyperglycemia to Suppress Endogenous Glucose ProductionDiabetes, 1996
- The regulatory protein of glucokinase binds to the hepatocyte matrix, but, unlike glucokinase, does not translocate during substrate stimulationBiochemical Journal, 1995
- Intracellular binding of glucokinase in hepatocytes and translocation by glucose, fructose and insulinBiochemical Journal, 1993
- Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridizationHistochemistry and Cell Biology, 1993
- Fructose 1‐phosphate and the regulation of glucokinase activity in isolated hepatocytesEuropean Journal of Biochemistry, 1990