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Angiotensin II exerts dual actions on sodium-glucose transporter 1-mediated transport in the human jejunal mucosa

Artikel i vetenskaplig tidskrift
Författare Anna Casselbrant
Mantas Malinauskas
Hanns-Ulrich Marschall
Ville Wallenius
Lars Fändriks
Publicerad i Scandinavian Journal of Gastroenterology
Volym 50
Nummer/häfte 9
Sidor 1068-1075
ISSN 0036-5521
Publiceringsår 2015
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för gastrokirurgisk forskning och utbildning
Institutionen för medicin, avdelningen för molekylär och klinisk medicin
Sidor 1068-1075
Språk en
Länkar dx.doi.org/10.3109/00365521.2015.10...
https://gup.ub.gu.se/file/169481
Ämnesord angiotensin II type 2 receptor, glucose transporters, human, intestinal, jejunum, renin-angiotensin, ussing chamber
Ämneskategorier Klinisk fysiologi

Sammanfattning

Objectives. Intestinal glucose absorption is mainly mediated via the sodium-glucose transporter 1 (SGLT1) at the apex of the enterocytes, whereas the glucose transporter 2 (GLUT2) provides a basolateral exit. It has been shown in rats that Angiotensin II (AngII), the principal mediator of renin-angiotensin system (RAS), inhibits jejunal SGLT1-mediated glucose absorption. The aim of the present study was to investigate if a similar mechanism exists also in the human jejunal mucosa. Material and methods. Enteroscopy with mucosal biopsy sampling was performed in 28 healthy volunteers. Functional assessments were performed in Ussing chambers using a pharmacological approach. Western blotting and immunohistochemistry were used to assess the presence of the AngII type 1 (AT1R) and type 2 receptor (AT2R), as well as the glucose transporters SGLT1 and GLUT2. Results. Exposure of the mucosa to 10 mM glucose elicited a »50% increase in the epithelium-generated current (Iep). This glucose-induced electrogenic response was sensitive to the competitive SGLT1 inhibitor phlorizin, but not to AngII when given alone. AngII combined with the AT2R blocker PD123319 markedly inhibited the response. AngII in combination with the AT1R antagonist losartan tended to increase the electrogenic response, whereas direct activation of AT2R using the agonist C21 significantly enhanced the mucosal response to glucose. The AT1R and AT2R as well as SGLT1 and GLUT2 were detected inside the human enterocytes. Conclusions. The pharmacological analysis indicated that activation of AT1R inhibits, whereas activation of AT2R enhances SGLT1-mediated glucose transport in the human jejunal mucosa.

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