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Publication
Novel stable isotope analyses demonstrate significant rates of glucose cycling
in mouse pancreatic islets.
Authors Wall ML, Pound LD, Trenary I, O'Brien RM, Young JD
Submitted By Jamey Young on 7/24/2015
Status Published
Journal Diabetes
Year 2015
Date Published 6/1/2015
Volume : Pages 64 : 2129 - 2137
PubMed Reference 25552595
Abstract 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.




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