title: Na(+)-D-glucose cotransporter SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion.
abstract: To clarify the physiological role of Na(+)-D-glucose cotransporter SGLT1 in small intestine and kidney, Sglt1(-/-) mice were generated and characterized phenotypically. After gavage of d-glucose, small intestinal glucose absorption across the brush-border membrane (BBM) via SGLT1 and GLUT2 were analyzed. Glucose-induced secretion of insulinotropic hormone (GIP) and glucagon-like peptide 1 (GLP-1) in wild-type and Sglt1(-/-) mice were compared. The impact of SGLT1 on renal glucose handling was investigated by micropuncture studies. It was observed that Sglt1(-/-) mice developed a glucose-galactose malabsorption syndrome but thrive normally when fed a glucose-galactose-free diet. In wild-type mice, passage of D-glucose across the intestinal BBM was predominantly mediated by SGLT1, independent the glucose load. High glucose concentrations increased the amounts of SGLT1 and GLUT2 in the BBM, and SGLT1 was required for upregulation of GLUT2. SGLT1 was located in luminal membranes of cells immunopositive for GIP and GLP-1, and Sglt1(-/-) mice exhibited reduced glucose-triggered GIP and GLP-1 levels. In the kidney, SGLT1 reabsorbed ∼3% of the filtered glucose under normoglycemic conditions. The data indicate that SGLT1 is 1) pivotal for intestinal mass absorption of d-glucose, 2) triggers the glucose-induced secretion of GIP and GLP-1, and 3) triggers the upregulation of GLUT2.
authors: Institute of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors: Valentin
authors: V
authors: Gorboulev
authors: Annette
authors: A
authors: Schürmann
authors: Volker
authors: V
authors: Vallon
authors: Helmut
authors: H
authors: Kipp
authors: Alexander
authors: A
authors: Jaschke
authors: Dirk
authors: D
authors: Klessen
authors: Alexandra
authors: A
authors: Friedrich
authors: Stephan
authors: S
authors: Scherneck
authors: Timo
authors: T
authors: Rieg
authors: Robyn
authors: R
authors: Cunard
authors: Maike
authors: M
authors: Veyhl-Wichmann
authors: Aruna
authors: A
authors: Srinivasan
authors: Daniela
authors: D
authors: Balen
authors: Davorka
authors: D
authors: Breljak
authors: Rexhep
authors: R
authors: Rexhepaj
authors: Helen E
authors: HE
authors: Parker
authors: Fiona M
authors: FM
authors: Gribble
authors: Frank
authors: F
authors: Reimann
authors: Florian
authors: F
authors: Lang
authors: Stefan
authors: S
authors: Wiese
authors: Ivan
authors: I
authors: Sabolic
authors: Michael
authors: M
authors: Sendtner
authors: Hermann
authors: H
authors: Koepsell
mesh_terms: D000818:Animals; D005260:Female; D005947:Glucose / Q000493:pharmacokinetics* / Q000494:pharmacology; D006029:Glycosuria / Q000378:metabolism; D054795:Incretins / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007408:Intestinal Absorption / Q000235:genetics*; D007421:Intestine, Small / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D054795:Incretins; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; D005947:Glucose