Novel Stable Isotope Analyses Demonstrate Significant Rates of Glucose Cycling in Mouse Pancreatic Islets
| Autor: | Jamey D. Young, Irina Trenary, Martha L. Wall, Lynley D. Pound, Richard M. O'Brien |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
endocrine system Endocrinology Diabetes and Metabolism Glucose uptake 030209 endocrinology & metabolism Carbohydrate metabolism In Vitro Techniques Gas Chromatography-Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Islets of Langerhans Mice 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Glycolysis 030304 developmental biology Mice Knockout 0303 health sciences geography geography.geographical_feature_category biology Glucokinase Pancreatic islets Islet Mice Inbred C57BL Endocrinology medicine.anatomical_structure Glucose L-Glucose chemistry Islet Studies Isotope Labeling biology.protein Glucose-6-Phosphatase Glucose 6-phosphatase |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | A polymorphism located in the G6PC2 gene, which encodes an islet-specific glucose-6-phosphatase catalytic subunit, is the most important common determinant of variations in fasting blood glucose (FBG) levels in humans. Studies of G6pc2 knockout (KO) mice suggest that G6pc2 represents a negative regulator of basal glucose-stimulated insulin secretion (GSIS) that acts by hydrolyzing glucose-6-phosphate (G6P), thereby reducing glycolytic flux. However, this conclusion conflicts with the very low estimates for the rate of glucose cycling in pancreatic islets, as assessed using radioisotopes. We have reassessed the rate of glucose cycling in pancreatic islets using a novel stable isotope method. The data show much higher levels of glucose cycling than previously reported. In 5 mmol/L glucose, islets from C57BL/6J chow-fed mice cycled ∼16% of net glucose uptake. The cycling rate was further increased at 11 mmol/L glucose. Similar cycling rates were observed using islets from high fat–fed mice. Importantly, glucose cycling was abolished in G6pc2 KO mouse islets, confirming that G6pc2 opposes the action of the glucose sensor glucokinase by hydrolyzing G6P. The demonstration of high rates of glucose cycling in pancreatic islets explains why G6pc2 deletion enhances GSIS and why variants in G6PC2 affect FBG in humans. |
| Databáze: | OpenAIRE |
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