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

Physiol Rep. 2018 Jan;6(1):e13562. doi: 10.14814/phy2.13562.

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 (Isc )). 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 Isc . SGLT1 phosphorylation was not inducible by Epi. Epi treatment decreased glucose-induced Isc and glucose flux rates in the jejunum but increased basal Isc 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.

Keywords: GLUT2; SGLT1; Ussing chamber; intestinal axis; intestinal glucose transport.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinase Kinases
  • Animals
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Epinephrine / pharmacology
  • Female
  • Glucose / metabolism*
  • Glucose Transporter Type 2 / metabolism
  • Intestinal Absorption
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Phosphorylation
  • Protein Kinases / metabolism
  • Protein Processing, Post-Translational
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism*
  • Swine

Substances

  • Glucose Transporter Type 2
  • Sodium-Glucose Transporter 1
  • Protein Kinases
  • Cyclic AMP-Dependent Protein Kinases
  • AMP-Activated Protein Kinase Kinases
  • Glucose
  • Epinephrine