Urinary excretion in mice after impairment of extracellular sugar detection. Metabolic and electrolyte levels in 24-h urine samples from wild-type (WT) or transgenic mice fed a standard or a glucose-rich diet. Values are presented as means±S.E.M. (n = 6 per group). Statistical differences between wild-type and transgenic mice are indicated as *P<0.05 ns non significant, nd indicates not determined.

<p>Urinary excretion in mice after impairment of extracellular sugar detection. Metabolic and electrolyte levels in 24-h urine samples from wild-type (WT) or transgenic mice fed a standard or a glucose-rich diet. Values are presented as means±S.E.M. (n = 6 per group). Statistical differences between wild-type and transgenic mice are indicated as *P<0.05 ns non significant, nd indicates not determined.</p

Impairment of extracellular sugar detection in GLUT2-expressing tissues in transgenic mice.

<p>Effect of a glucose-rich diet on gene expression in liver (A) and adipose tissue (C). Transgenic (Tg) and wild-type (WT) mice were fasted for 48 h and refed for 15 h before liver and epididymal fat pad biopsies. Levels of mRNA were analyzed by real time PCR. Values are presented as means±S.E.M. (n = 3 to 5 mice/group). Statistical differences between refed and fasted mice are indicated by *P<0.05, **P<0.01, and ns non significant. B: GLUT2 protein levels in total membrane preparations from the liver of mice fed a glucose-rich diet for five days. D: Blood glucose concentrations during an insulin tolerance test in wild-type and transgenic mice. Values are presented as means±S.E.M (n = 8 to 10 mice/group).</p

Kidney function in mice after impairment of extracellular sugar detection.

<p>A: Effect of a glucose-rich diet on gene expression in the kidney of transgenic (Tg) and wild-type (WT) mice fasted for 48 h and refed for 15 h. Levels of mRNA were analyzed by real-time PCR. Values are presented as means±S.E.M. (n = 3 to 4 mice/group). Statistical differences between refed and fasted mice are indicated as *P<0.05, **P<0.01 and ns non significant. B: GLUT2 protein levels in total membrane preparations of kidney from mice fed with a glucose-rich diet for five days. C: Structure, size and weight of kidneys from wild-type and transgenic mice shown by ultrasonic image (transverse cross section). D: Urine and blood glucose concentrations during an oral glucose tolerance test in fasted wild-type and transgenic mice (n = 3 mice per group). Statistical differences between transgenic and wild-type mice are indicated as **P<0.01 (two-way ANOVA) for the areas under the curves. E: Levels of SGLT mRNA were analyzed by real-time PCR. Values are presented as means±S.E.M. (n = 3 to 4 mice/group). Statistical differences between refed and fasted mice are indicated as **P<0.01 and ns non significant.</p

Generation of GLUT2-loop transgenic mice.

<p>A: Quantification of the transgene copy number in genomic DNA from independent lines of mice (Tg G, P, B and W) to the reference gene Apolipoprotein A1 (ApoA1). B: RT-PCR analysis of transgene and L19 control mRNA levels in various tissues. C: Immunoprecipitation and immunoblot analysis showing the presence of GLUT2 loop in liver homogenate from transgenic mice.</p

Pancreatic function in mice after impairment of extracellular sugar detection.

<p>A: Effect of a glucose-rich diet on gene expression in the pancreas of wild-type (WT) and transgenic (Tg) mice fasted for 48h and refed for 15 h. Levels of mRNA were analyzed by real-time PCR. Values are presented as means±S.E.M. (n = 3 to 4 mice/group). Statistical differences between refed and fasted mice are indicated as **P<0.01 and ns non significant. B: GLUT2 protein levels in total membrane preparations of pancreas from mice fed a glucose-rich diet for five days. C: Left panel: Blood glucose concentrations during an oral glucose tolerance test in wild-type and transgenic mice fasted for 24 h (n = 17 for wild-type mice, n = 2 to 5 for transgenic mice). Statistical differences between transgenic and wild-type mice are indicated as ***P<0.001, *P<0.05 and ns non significant (two-way ANOVA) for the areas under the curves. Right panel: Blood glucose concentrations in wild-type and transgenic mice in the fasted state or 6 h after being refed with a glucose-rich diet. Values are presented as means±S.E.M. (n = 4 to 8 mice/group). D: Upper panel: Plasma insulin concentrations during an oral glucose tolerance test in fasted wild-type and transgenic mice (n = 10 to 13 mice/group). Statistical differences between transgenic and wild-type mice are indicated as ***P<0.001 (two-way ANOVA) for the areas under the curves. Lower panel: Pancreatic insulin content in mice 6h after being refed a standard diet. Values are presented as means±S.E.M. (n = 5 mice/group). Statistical differences between transgenic and wild-type mice are indicated as *P<0.05. E: Upper panel : Representative immunostaining with antibody against insulin of pancreatic sections from wild-type and transgenic mice. Arrows indicate small islets. The bar corresponds to 100 µm. Lower panel: Histomorphometric comparisons of islet number, size and ß-cell mass. Proportion of small islets (<25 µm) to total number of islets is statistically different indicated as *P<0.03 between transgenic and wild-type mice.</p