title: Cardiotrophin-1 decreases intestinal sugar uptake in mice and in Caco-2 cells.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: M
authors.initials: M
authors.lastname: López-Yoldi
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Castilla-Madrigal
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.
authors.forename: M P
authors.initials: MP
authors.lastname: Lostao
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Barber
authors.affiliation: Department of Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona, Navarra, Spain.|CIBERehd, Institute of Health Carlos III, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Prieto
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.|CIBERobn, Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Martínez
authors.affiliation: Department of Gene Therapy and Hepatology, CIMA, University of Navarra, Pamplona, Navarra, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Bustos
authors.affiliation: Department of Nutrition, Food Science and Physiology, University of Navarra, Pamplona, Navarra, Spain.|Centre for Nutrition Research, University of Navarra, Pamplona, Navarra, Spain.|IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.|CIBERobn, Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018938:Caco-2 Cells; D016207:Cytokines / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008757:Methylglucosides / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D012265:Ribonucleotides / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000096:biosynthesis / Q000235:genetics; D000073893:Sugars / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007004:Hypoglycemic Agents; D008757:Methylglucosides; D012265:Ribonucleotides; D050796:STAT3 Transcription Factor; C495675:Slc5a1 protein, mouse; D051269:Sodium-Glucose Transporter 1; C494087:Stat3 protein, mouse; D000073893:Sugars; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D000620:Aminoimidazole Carboxamide; C027020:methylglucoside; C092073:cardiotrophin 1; C031143:AICA ribonucleotide
keywords: AMPK; Caco-2 cells; Cardiotrophin-1; SGLT-1; everted intestinal rings; sugar uptake