Degree of SGLT1 phosphorylation is associated with but does not determine segment-specific glucose transport features in the porcine small intestines.

Stefanie Klinger,Elisabeth Brandt,Gerhard Breves,Patrick Lange,Bernd Schröder,Karin Hustedt,Jens Herrmann

doi:10.14814/phy2.13562

Stefanie Klinger, Elisabeth Brandt + Show 5 more

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https://doi.org/10.14814/phy2.13562

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Abstract

Glucose‐induced electrogenic ion transport is higher in the porcine ileum compared with the jejunum despite equal apical abundance of SGLT1. The objective of this study was a detailed determination of SGLT1 and GLUT2 expressions at mRNA and protein levels along the porcine small intestinal axis. Phosphorylation of SGLT1 at serine 418 was assessed as a potential modulator of activity. Porcine intestinal tissues taken along the intestinal axis 1 h or 3 h after feeding were analyzed for relative mRNA (RT‐PCR) and protein levels (immunoblot) of SGLT1, pSGLT1, GLUT2, (p)AMPK, β2‐receptor, and PKA substrates. Functional studies on electrogenic glucose transport were done (Ussing chambers: short circuit currents (I sc)). Additionally, effects of epinephrine (Epi) administration on segment‐specific glucose transport and pSGLT1 content were examined. SGLT1 and GLUT2 expression was similar throughout the small intestines but lower in the duodenum and distal ileum. pSGLT1 abundance was significantly lower in the ileum compared with the jejunum associated with significantly higher glucose‐induced I sc. SGLT1 phosphorylation was not inducible by Epi. Epi treatment decreased glucose‐induced I sc and glucose flux rates in the jejunum but increased basal I sc in the ileum. Epi‐induced PKA activation was detectable in jejunal tissue. These results may indicate that SGLT1 phosphorylation at Ser418 represents a structural change to compensate for certain conditions that may decrease glucose transport (unfavorable driving forces/changed apical membrane potential) rather than being the cause for the overall differences in glucose transport characteristics between the jejunum and ileum.

Highlights

IntroductionThe small intestines of monogastric animals are the major sites for absorption of nutrients such as fatty acids, amino acids, and monosaccharides
The objective of this study was a detailed determination of SGLT1 and glucose transporter 2 (GLUT2) expressions at mRNA and protein levels along the porcine small intestinal axis
In contrast to mice(Yoshikawa et al 2011) or horses(Dyer et al 2009), in the 1 h-pigs, the abundance of SGLT1 mRNA was lowest in the duodenum and, whereas murine SGLT1 abundance decreases along the small intestinal axis, in the porcine small intestines, SGLT1 presence was similar throughout the whole jejunum and the proximal ileum

Summary

Introduction

The small intestines of monogastric animals are the major sites for absorption of nutrients such as fatty acids, amino acids, and monosaccharides. Among the latter, glucose represents the most abundant molecule. According to the classical model, glucose uptake from the intestinal lumen into the enterocytes is mediated by the Na+/glucose cotransporter 1 (SGLT1) as a secondary active, electrogenic transport system, while intracellularly accumulated glucose is released by facilitated diffusion via the basolateral located glucose transporter 2 (GLUT2) (Wright et al.2007). According to the Pappenheimer hypothesis, solvent drag driven paracellular glucose transport exceeds transcellular transport at high glucose availability (Pappenheimer and Reiss 1987)

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