Cardiotrophin-1 decreases intestinal sugar uptake in mice and in Caco-2 cells

Autores: López Yoldi, Miguel; Castilla Madrigal, Rosa María; Lostao Crespo, María del Pilar; Barber Cárcamo, Ana María; Prieto Valtueña, Jesús María; Martínez Hernández, Alfredo; Bustos de Abajo, Matilde; Moreno Aliaga, María Jesús
Título de la revista: ACTA PHYSIOLOGICA
ISSN: 1748-1708
Volumen: 217
Número: 3
Páginas: 217 - 226
Fecha de publicación: 2016
rCT-1 effects on ¿-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 ¿-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 ¿-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 ¿-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 ¿-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.