Journal Article

Na+- d -glucose Cotransporter SGLT1 is Pivotal for Intestinal Glucose Absorption and Glucose-Dependent Incretin Secretion

Gorboulev, Valentin, Rexhepaj, Rexhep, Sendtner, Michael, Wiese, Stefan, Friedrich, Alexandra, Reimann, Frank, Cunard, Robyn, Breljak, Davorka, Jaschke, Alexander, Kipp, Helmut, Lang, Florian, Srinivasan, Aruna, Parker, Helen E., Scherneck, Stephan, Gribble, Fiona M., Rieg, Timo, Sabolic, Ivan, Koepsell, Hermann, Schürmann, Annette, Klessen, Dirk, Veyhl-Wichmann, Maike, Balen, Daniela, Vallon, Volker

2012

Overview

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.

• Publisher: American Diabetes Association
• Subject: Animals / Biological and medical sciences / Diabetes / Diabetes. Impaired glucose tolerance / Diet / Dietary minerals / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Glucagon / Glucose / Glucose - pharmacokinetics / Glucose - pharmacology / Glycosuria - metabolism / Incretins - metabolism / Insulin / Insulin-Secreting Cells - drug effects / Insulin-Secreting Cells - metabolism / Intestinal Absorption - genetics / Intestine, Small - metabolism / Kidney Tubules, Proximal - drug effects / Kidney Tubules, Proximal - metabolism / Lasers / Male / Medical sciences / Metabolism / Mice / Mice, Inbred C57BL / Mice, Knockout / Oocytes - drug effects / Oocytes - metabolism / Pathophysiology / Peptides / Physiology / Small intestine / Sodium-Glucose Transporter 1 - genetics / Sodium-Glucose Transporter 1 - metabolism / Sodium-Glucose Transporter 1 - physiology