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The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.

Röder PV, Geillinger KE, Zietek TS, Thorens B, Koepsell H, Daniel H - PLoS ONE (2014)

Bottom Line: Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose.GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration.Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

View Article: PubMed Central - PubMed

Affiliation: ZIEL Research Center for Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, Freising, Bavaria, Germany.

ABSTRACT
Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

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Increases in plasma GIP and GLP-1 levels after intragastric glucose are abolished in SGLT1-deficient mice.Sglt1+/+ and sglt1−/− mice were challenged with an oral glucose gavage (4 g/kg). Plasma GIP, GLP-1 and insulin hormone levels were measured before (white bars) and 15 minutes after the bolus (plaid bars). (A) Total GIP concentrations in the fasting state (basal) and after glucose gavage. (B) Active GLP-1 concentrations in the fasting state and after glucose gavage. (C) Insulin concentrations in the fasting state and after gavage. Values are expressed as mean ± SEM. Statistical analyses were performed using 2-way ANOVA with Bonferroni post-test. * p<0.05, ** p<0.01, *** p<0.001. N = 3–8 mice per group.
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pone-0089977-g002: Increases in plasma GIP and GLP-1 levels after intragastric glucose are abolished in SGLT1-deficient mice.Sglt1+/+ and sglt1−/− mice were challenged with an oral glucose gavage (4 g/kg). Plasma GIP, GLP-1 and insulin hormone levels were measured before (white bars) and 15 minutes after the bolus (plaid bars). (A) Total GIP concentrations in the fasting state (basal) and after glucose gavage. (B) Active GLP-1 concentrations in the fasting state and after glucose gavage. (C) Insulin concentrations in the fasting state and after gavage. Values are expressed as mean ± SEM. Statistical analyses were performed using 2-way ANOVA with Bonferroni post-test. * p<0.05, ** p<0.01, *** p<0.001. N = 3–8 mice per group.

Mentions: After the glucose gavage, there was a more than 5-fold increase in plasma GIP levels in sglt1+/+ mice when compared to basal levels; this response to glucose however, was completely abolished in sglt1−/− mice (Fig. 2A). Plasma GLP-1 concentrations increased around 10-fold after gavage in sglt1+/+ but not in sglt1−/− animals (Fig. 2B). Plasma insulin levels following the glucose bolus were reduced by 36% in sglt1−/− as compared to sglt1+/+ mice with a 1.7-fold increase as compared to basal levels (Fig. 2C). The abolition of GIP and GLP-1 responses in sglt1−/− mice demonstrate the pivotal role of SGLT1 also in intestinal incretin secretion. Despite the lack of incretin stimulation, insulin levels changed only modestly but this has also been observed previously [5].


The role of SGLT1 and GLUT2 in intestinal glucose transport and sensing.

Röder PV, Geillinger KE, Zietek TS, Thorens B, Koepsell H, Daniel H - PLoS ONE (2014)

Increases in plasma GIP and GLP-1 levels after intragastric glucose are abolished in SGLT1-deficient mice.Sglt1+/+ and sglt1−/− mice were challenged with an oral glucose gavage (4 g/kg). Plasma GIP, GLP-1 and insulin hormone levels were measured before (white bars) and 15 minutes after the bolus (plaid bars). (A) Total GIP concentrations in the fasting state (basal) and after glucose gavage. (B) Active GLP-1 concentrations in the fasting state and after glucose gavage. (C) Insulin concentrations in the fasting state and after gavage. Values are expressed as mean ± SEM. Statistical analyses were performed using 2-way ANOVA with Bonferroni post-test. * p<0.05, ** p<0.01, *** p<0.001. N = 3–8 mice per group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3935955&req=5

pone-0089977-g002: Increases in plasma GIP and GLP-1 levels after intragastric glucose are abolished in SGLT1-deficient mice.Sglt1+/+ and sglt1−/− mice were challenged with an oral glucose gavage (4 g/kg). Plasma GIP, GLP-1 and insulin hormone levels were measured before (white bars) and 15 minutes after the bolus (plaid bars). (A) Total GIP concentrations in the fasting state (basal) and after glucose gavage. (B) Active GLP-1 concentrations in the fasting state and after glucose gavage. (C) Insulin concentrations in the fasting state and after gavage. Values are expressed as mean ± SEM. Statistical analyses were performed using 2-way ANOVA with Bonferroni post-test. * p<0.05, ** p<0.01, *** p<0.001. N = 3–8 mice per group.
Mentions: After the glucose gavage, there was a more than 5-fold increase in plasma GIP levels in sglt1+/+ mice when compared to basal levels; this response to glucose however, was completely abolished in sglt1−/− mice (Fig. 2A). Plasma GLP-1 concentrations increased around 10-fold after gavage in sglt1+/+ but not in sglt1−/− animals (Fig. 2B). Plasma insulin levels following the glucose bolus were reduced by 36% in sglt1−/− as compared to sglt1+/+ mice with a 1.7-fold increase as compared to basal levels (Fig. 2C). The abolition of GIP and GLP-1 responses in sglt1−/− mice demonstrate the pivotal role of SGLT1 also in intestinal incretin secretion. Despite the lack of incretin stimulation, insulin levels changed only modestly but this has also been observed previously [5].

Bottom Line: Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose.GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration.Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

View Article: PubMed Central - PubMed

Affiliation: ZIEL Research Center for Nutrition and Food Sciences, Biochemistry Unit, Technische Universität München, Freising, Bavaria, Germany.

ABSTRACT
Intestinal glucose absorption is mediated by SGLT1 whereas GLUT2 is considered to provide basolateral exit. Recently, it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Moreover, SGLT1 and GLUT2 are suggested to play an important role in intestinal glucose sensing and incretin secretion. In mice that lack either SGLT1 or GLUT2 we re-assessed the role of these transporters in intestinal glucose uptake after radiotracer glucose gavage and performed Western blot analysis for transporter abundance in apical membrane fractions in a comparative approach. Moreover, we examined the contribution of these transporters to glucose-induced changes in plasma GIP, GLP-1 and insulin levels. In mice lacking SGLT1, tissue retention of tracer glucose was drastically reduced throughout the entire small intestine whereas GLUT2-deficient animals exhibited higher tracer contents in tissue samples than wild type animals. Deletion of SGLT1 resulted also in reduced blood glucose elevations and abolished GIP and GLP-1 secretion in response to glucose. In mice lacking GLUT2, glucose-induced insulin but not incretin secretion was impaired. Western blot analysis revealed unchanged protein levels of SGLT1 after glucose gavage. GLUT2 detected in apical membrane fractions mainly resulted from contamination with basolateral membranes but did not change in density after glucose administration. SGLT1 is unequivocally the prime intestinal glucose transporter even at high luminal glucose concentrations. Moreover, SGLT1 mediates glucose-induced incretin secretion. Our studies do not provide evidence for GLUT2 playing any role in either apical glucose influx or incretin secretion.

Show MeSH
Related in: MedlinePlus