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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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Deletion of SGLT1 results in reduced glucose contents in intestinal tissues and blood.Sglt1+/+ (white bars) and sglt1−/− mice (black bars) received an intragastric glucose bolus (4 g/kg) containing radiolabeled D-glucose. After 15 minutes, radiotracer contents in intestinal tissue samples covering the entire small intestine, in plasma as well as blood glucose was measured. (A) Tissue profiling for glucose tracer contents along the small intestine of sglt1+/+ and sglt1−/− mice. (B) Average accumulation of glucose tracer amounts in 1 cm intestinal tissue samples over 15 minutes. (C) Radiolabeled glucose contents in plasma. (D) Increase in blood glucose after glucose gavage. Values are expressed as mean ± SEM. Statistical analyses for glucose tracer in tissues and plasma were performed using unpaired t-test with Welch’s correction. ** p<0.01. Values of rise in blood glucose are expressed as mean ± SEM. Statistical analyses were performed using unpaired t-test. * p<0.05. N = 4–5 mice per group.
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pone-0089977-g001: Deletion of SGLT1 results in reduced glucose contents in intestinal tissues and blood.Sglt1+/+ (white bars) and sglt1−/− mice (black bars) received an intragastric glucose bolus (4 g/kg) containing radiolabeled D-glucose. After 15 minutes, radiotracer contents in intestinal tissue samples covering the entire small intestine, in plasma as well as blood glucose was measured. (A) Tissue profiling for glucose tracer contents along the small intestine of sglt1+/+ and sglt1−/− mice. (B) Average accumulation of glucose tracer amounts in 1 cm intestinal tissue samples over 15 minutes. (C) Radiolabeled glucose contents in plasma. (D) Increase in blood glucose after glucose gavage. Values are expressed as mean ± SEM. Statistical analyses for glucose tracer in tissues and plasma were performed using unpaired t-test with Welch’s correction. ** p<0.01. Values of rise in blood glucose are expressed as mean ± SEM. Statistical analyses were performed using unpaired t-test. * p<0.05. N = 4–5 mice per group.

Mentions: Animals lacking SGLT1 displayed significantly decreased glucose tracer contents in all segments of the intestine after the gavage when compared to wild type mice (Fig. 1A). The reduction accounted for 80% (Fig. 1B), confirming the prime role of SGLT1 in intestinal glucose absorption. The amount of radiotracer in plasma was reduced by 73% when compared to wild type animals (Fig. 1C) as was the rise in blood glucose levels (Fig. 1D).


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)

Deletion of SGLT1 results in reduced glucose contents in intestinal tissues and blood.Sglt1+/+ (white bars) and sglt1−/− mice (black bars) received an intragastric glucose bolus (4 g/kg) containing radiolabeled D-glucose. After 15 minutes, radiotracer contents in intestinal tissue samples covering the entire small intestine, in plasma as well as blood glucose was measured. (A) Tissue profiling for glucose tracer contents along the small intestine of sglt1+/+ and sglt1−/− mice. (B) Average accumulation of glucose tracer amounts in 1 cm intestinal tissue samples over 15 minutes. (C) Radiolabeled glucose contents in plasma. (D) Increase in blood glucose after glucose gavage. Values are expressed as mean ± SEM. Statistical analyses for glucose tracer in tissues and plasma were performed using unpaired t-test with Welch’s correction. ** p<0.01. Values of rise in blood glucose are expressed as mean ± SEM. Statistical analyses were performed using unpaired t-test. * p<0.05. N = 4–5 mice per group.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0089977-g001: Deletion of SGLT1 results in reduced glucose contents in intestinal tissues and blood.Sglt1+/+ (white bars) and sglt1−/− mice (black bars) received an intragastric glucose bolus (4 g/kg) containing radiolabeled D-glucose. After 15 minutes, radiotracer contents in intestinal tissue samples covering the entire small intestine, in plasma as well as blood glucose was measured. (A) Tissue profiling for glucose tracer contents along the small intestine of sglt1+/+ and sglt1−/− mice. (B) Average accumulation of glucose tracer amounts in 1 cm intestinal tissue samples over 15 minutes. (C) Radiolabeled glucose contents in plasma. (D) Increase in blood glucose after glucose gavage. Values are expressed as mean ± SEM. Statistical analyses for glucose tracer in tissues and plasma were performed using unpaired t-test with Welch’s correction. ** p<0.01. Values of rise in blood glucose are expressed as mean ± SEM. Statistical analyses were performed using unpaired t-test. * p<0.05. N = 4–5 mice per group.
Mentions: Animals lacking SGLT1 displayed significantly decreased glucose tracer contents in all segments of the intestine after the gavage when compared to wild type mice (Fig. 1A). The reduction accounted for 80% (Fig. 1B), confirming the prime role of SGLT1 in intestinal glucose absorption. The amount of radiotracer in plasma was reduced by 73% when compared to wild type animals (Fig. 1C) as was the rise in blood glucose levels (Fig. 1D).

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