Glucose transporters in the small intestine in health and disease

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.

Bioaccessibility and In Vitro Intestinal Permeability of a Recombinant Lectin from Tepary Bean (Phaseolus acutifolius) Using the Everted Intestine Assay

“…When the concentration of glucose is low in the intestinal lumen, only SGLT1 is located in the apical side to transport it. Nonetheless, if the glucose concentration is high, GLUT2 is also located in the apical side to support glucose absorption [ 28 ]. Glucose enters from the apical side to the basolateral side of the small intestine, confirming the functionality of the glucose transporters and the gut sacs’ viability [ 29 , 30 ].…”

“…Glucose enters from the apical side to the basolateral side of the small intestine, confirming the functionality of the glucose transporters and the gut sacs’ viability [ 29 , 30 ]. However, if GLUT2 is located on the apical side, a low opposite glucose transport is observed [ 28 ] ( Figure 1 A).…”

Intestinal stem cell-derived enteroids from morbidly obese patients preserve obesity-related phenotypes: Elevated glucose absorption and gluconeogenesis

“…Interestingly, we observed significant differences in glucose absorption between enteroids from the BS naïve lean subjects and those from the post-BS patients, despite the lack of significant differences in the expression levels of sugar transporters between these two groups. Additional consideration for differences in signaling, intracellular localization, and subcellular trafficking could contribute to different glucose-absorption profiles [ 23 , 59 ]. Dynamic regulation of glucose transport by protein trafficking has been reported for GLUT4 [ 60 ].…”

Regulation of Gastrointestinal Immunity by Metabolites

“…Dietary carbohydrates are digested in the small intestine into glucose, galactose, and fructose and then absorbed by enterocytes. Sodium–glucose co-transporter (SGLT)1, glucose transporter (GLUT)5, and GLUT2 are responsible for the transport of glucose, galactose, and fructose across the brush border membrane or basolateral membrane [ 70 ]. A loss-of-function study using a gene knock out mouse model suggested that SGLT1 is important for fast glucose absorption; however, the presence of GLUT2 has not been shown to have any role in either apical glucose influx or incretin secretion [ 71 ].…”