Cardiotrophin-1 decreases intestinal sugar uptake in mice and in Caco-2 cells
Aim Cardiotrophin‐1 (CT‐1) is a member of the IL‐6 family of cytokines with a key role in glucose and lipid metabolism. In the current investigation, we examined the in vivo and in vitro effects of CT‐1 treatment on intestinal sugar absorption in different experimental models. Methods rCT‐1 effects...
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Published in | Acta Physiologica Vol. 217; no. 3; pp. 217 - 226 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.07.2016
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Aim
Cardiotrophin‐1 (CT‐1) is a member of the IL‐6 family of cytokines with a key role in glucose and lipid metabolism. In the current investigation, we examined the in vivo and in vitro effects of CT‐1 treatment on intestinal sugar absorption in different experimental models.
Methods
rCT‐1 effects on α‐Methyl‐D‐glucoside uptake were assessed in everted intestinal rings from wild‐type and CT‐1−/− mice and in Caco‐2 cells. rCT‐1 actions on SGLT‐1 expression in brush border membrane vesicles and the identification of the potential signalling pathways involved were determined by Western blot.
Results
In vivo administration (0.2 mg kg−1) of rCT‐1 caused a significant decrease on α‐Methyl‐D‐glucoside uptake in everted intestinal rings from wild‐type and CT‐1−/− mice after short‐term and long‐term treatments. Similarly, in vitro treatment (1–50 ng mL−1) with rCT‐1 reduced α‐Methyl‐D‐glucoside uptake in everted intestinal rings. In Caco‐2 cells, rCT‐1 treatment (20 ng mL−1, 1 and 24 h) lowered apical uptake of α‐Methyl‐D‐glucoside in parallel with a decrease on SGLT‐1 protein expression. rCT‐1 promoted the phosphorylation of STAT‐3 after 5 and 15 min treatment, but inhibited the activation by phosphorylation of AMPK after 30 and 60 min. Interestingly, pre‐treatment with the JAK/STAT inhibitor (AG490) and with the AMPK activator (AICAR) reversed the inhibitory effects of rCT‐1 on α‐Methyl‐D‐glucoside uptake. AICAR also prevented the inhibition of SGLT‐1 observed in rCT‐1‐treated cells.
Conclusions
CT‐1 inhibits intestinal sugar absorption by the reduction of SGLT‐1 levels through the AMPK pathway, which could also contribute to explain the hypoglycaemic and anti‐obesity properties of CT‐1. |
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Bibliography: | istex:8E7C953C1B3C79F98F86F7DA0020B27F1E6ACAE0 ArticleID:APHA12674 ark:/67375/WNG-RKS7J2JX-H FIS - No. PI10/01516; No. PI13/01851 CIBERobn Asociación de Amigos University of Navarra Government of Navarra (Department of Health) Mutua Madrileña Foundation Línea Especial 'Nutrición, Obesidad y Salud' and Centre for Nutrition Research, Universidad de Navarra ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1748-1708 1748-1716 |
DOI: | 10.1111/apha.12674 |