Figure 1.
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.
Figure 2.
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.
Figure 3.
Animals lacking GLUT2 display higher tissue glucose contents but reduced amounts in blood.
Glut2+/+ (white bars) and glut2−/− mice (black bars) were administered an intragastric glucose bolus (4 g/kg) containing radiolabeled D-glucose. After 15 minutes, radiotracer content in intestinal tissue samples covering the whole small intestine, in plasma as well as blood glucose was measured. (A) Tissue radiotracer profile from proximal to distal small intestine in glut2+/+ and glut2−/− animals. (B) Average accumulation of glucose tracer per 1 cm segment over 15 minutes. (C) Plasma tracer contents. (D) Increase in blood glucose levels after glucose load. Values are expressed as mean ± SEM. Statistical analyses were performed using unpaired t-test. * p<0.05, ** p<0.01. N = 5–6 mice per group.
Figure 4.
Absence of GLUT2 affects insulin secretion but not GIP or GLP-1 levels after glucose gavage.
In glut2+/+ and glut2−/− mice receiving an oral glucose gavage (4 g/kg) plasma levels of GIP, GLP-1 and insulin 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 glucose gavage. Values are expressed as mean ± SEM. Statistical analyses were performed using 2-way ANOVA with Bonferroni post-test for comparison of GIP and insulin concentrations. # p<0.05, *** p<0.001. 2-way ANOVA was used for comparison of GLP-1 levels. * p<0.05. N = 3–4 mice per group.
Table 1.
Protein density of SGLT1 in brush border membranes of sglt1 and glut2 wild type mice and appopriate knockout littermates.
Table 2.
Protein density of GLUT2 in brush border membranes of sglt1 and glut2 wild type mice and appropriate knockout littermates.
Figure 5.
SGLT1 is located in the apical membrane.
Jejunal samples from sglt1+/+ mice before and after glucose gavage, respectively, as well as from and sglt1−/− littermates were stained for SGLT1 (red). Nuclei were stained with DAPI (blue). Apical localization of SGLT1 in sglt1+/+ mice (A) before and (B) after glucose challenge and in (C) sglt1−/− littermates.
Figure 6.
GLUT2 is not located in the apical but basolateral membrane.
Jejunal samples from glut2+/+ animals before and after glucose gavage, respectively, as well as from glut2−/− littermates were stained for GLUT2 (red). Nuclei were stained with DAPI (blue). Basolateral localization (arrows) of GLUT2 in glut2+/+ mice (A) in the basal state and (B) after glucose administration. (C) GLUT2 staining is absent in glut2−/− littermates.