Glucose transporters in the small intestine in health and disease
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INVITED REVIEW
Glucose transporters in the small intestine in health and disease Hermann Koepsell 1 Received: 5 February 2020 / Revised: 11 July 2020 / Accepted: 17 July 2020 # The Author(s) 2020
Abstract Absorption of monosaccharides is mainly mediated by Na+-D-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of D-glucose and D-galactose while GLUT5 is relevant for D-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane (BLM) or the BBM plus BLM at low and high luminal D-glucose concentrations, respectively. At high luminal D-glucose, the abundance SGLT1 in the BBM is increased. Hence, D-glucose absorption at low luminal glucose is mediated via SGLT1 in the BBM and GLUT2 in the BLM whereas high-capacity D-glucose absorption at high luminal glucose is mediated by SGLT1 plus GLUT2 in the BBM and GLUT2 in the BLM. The review describes functions and regulations of SGLT1, GLUT2, and GLUT5 in the small intestine including diurnal variations and carbohydrate-dependent regulations. Also, the roles of SGLT1 and GLUT2 for secretion of enterohormones are discussed. Furthermore, diseases are described that are caused by malfunctions of small intestinal monosaccharide transporters, such as glucose-galactose malabsorption, Fanconi syndrome, and fructose intolerance. Moreover, it is reported how diabetes, small intestinal inflammation, parental nutrition, bariatric surgery, and metformin treatment affect expression of monosaccharide transporters in the small intestine. Finally, food components that decrease D-glucose absorption and drugs in development that inhibit or downregulate SGLT1 in the small intestine are compiled. Models for regulations and combined functions of glucose transporters, and for interplay between D-fructose transport and metabolism, are discussed. Keywords Glucose transporter . Small intestine . Regulation . SGLT1 . GLUT2 . GLUT5 . Glucose-galactose malabsorption . Fructose intolerance . Diabetes . Bariatric surgery
Abbreviations Akt2 RAC-beta serine/threonine-protein ALDOB Aldolase B AMG α-Methyl-D-glucoside AMPK AMP-stimulated protein kinase BBB Brush border membrane BLM Basolateral membrane BMAL Brain and muscle arnt-like protein CBP cAMP response element protein– binding protein CCK Cholecystokinin
This article is part of the special issue on Glucose Transporters in Health and Disease in Pflügers Archiv—European Journal of Physiology * Hermann Koepsell [email protected] 1
Institute for Anatomy and Cell Biology, University of Würzburg, Koellikerstr 6, 97070 Würzburg, Germany
ChREBP CRE CREB DJB DNJ 2-DOG DXR EEC EGF EGFR ER FBS 2-[18F]DG FGID 5-FU GIP GLP-1 GLP-2 GGM
Carbohydrate-responsive element– binding protein cAMP response element cAMP response element–binding protein Duodeno-jejunal bypass 1-Deoxynojirimycin 2-Deoxy-D-glucose Doxorubicin Enteroendocine cell Epithelial growth factor Epithelial growth facto
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