An increased flux through the glucose 6-phosphate pool in enterocytes delays glucose absorption in Fxr-/- mice.
The farnesoid X receptor (FXR) is involved in regulation of bile acid and lipid metabolism. Recently, a role for FXR in control of glucose metabolism became evident. Because FXR is expressed along the length of the small intestine, we evaluated the potential role of FXR in glucose absorption and processing. During intravenous infusion of a trace amount of d-[6,6-(2)H(2)]glucose, a d-[U-(13)C]glucose-enriched oral glucose bolus was given, and glucose kinetics were determined in wild-type and Fxr(-/-) mice. Compared with wild-type mice, Fxr(-/-) mice showed a delayed plasma appearance of orally administered glucose. Multicompartmental kinetic modeling revealed that this delay was caused by an increased flux through the glucose 6-phosphate pool in enterocytes. Thus, our results show involvement of FXR in intestinal glucose absorption, representing a novel physiological function for this nuclear receptor.
van Dijk
Theo H
TH
Departments of Laboratory Medicine and Pediatrics, Center for Liver Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands.
Grefhorst
Aldo
A
Oosterveer
Maaike H
MH
Bloks
Vincent W
VW
Staels
Bart
B
Reijngoud
Dirk-Jan
DJ
Kuipers
Folkert
F
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D019298:Glucose-6-Phosphate / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D005947:Glucose; D019298:Glucose-6-Phosphate; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000099150:Receptor, Farnesoid X-Activated