Journal
DIABETES
Volume 61, Issue 1, Pages 187-196Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db11-1029
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Funding
- Deutsche Forschungsgemeinschaft [SFB 487/C1, DA 190/10-1, SFB 487/C4]
- National Institutes of Health [R0IDK56248, R01HL094728, R01DK28602, P30DK079337]
- American Heart Association [GRNT3440038, 10SDG2610034]
- American Society of Nephrology
- Department of Veterans Affairs
- Ministry for Science, Education and Sports of the Republic of Croatia [022-0222148-2146]
- Wellcome Trust [WT088357, WT084210]
- MRC Centre for Obesity and Related Metabolic Diseases
- Medical Research Council [G0600717B] Funding Source: researchfish
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL094728] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK079337, R01DK028602, R01DK056248] Funding Source: NIH RePORTER
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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, hi the kidney, SGLT1 re-absorbed similar to 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. Diabetes 61:187-196, 2012
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