Degree of SGLT1 phosphorylation is associated with but does not determine segment‐specific glucose transport features in the porcine small intestines. Issue 1 (15th January 2018)

• Record Type: Journal Article
• Authors: Klinger, Stefanie; Lange, Patrick; Brandt, Elisabeth; Hustedt, Karin; Schröder, Bernd; Breves, Gerhard; Herrmann, Jens
• Is Part Of: Physiological reports. Volume 6:Issue 1(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-01-15
• Subjects: GLUT2 -- intestinal axis -- intestinal glucose transport -- SGLT1 -- Ussing chamber; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13562
• Languages: English
• ISSNs: 2051-817X

Abstract

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. Abstract : Since the expression of proteins involved in intestinal glucose absorption along the intestinal axis in pigs is not well characterized and the reasons for the known regional differences in the SGLT1‐mediated glucose transport in the porcine small intestines are not clear, this study aimed at characterizing the expression of SGLT1 and GLUT2 on mRNA and protein levels in the porcine small intestines at different locations and after different time points after feeding in addition to functional data from Usssing chamber studies. Furthermore, the phosphorylation level of SGLT1 at Serin 418 was investigated for the first time in different intestinal segments and regulatory mechanisms were studied by incubating tissues with epinephrine. The results indicate, among other aspects, that the distrubution of SGLT1 in the porcine small intestines differs from rodents and that the phosphorylation level of SGLT1 differs along the intestinal axis but that this is not the reason for the observed functional regional differences.