Resistin-like molecule-beta inhibits SGLT-1 activity and enhances GLUT2-dependent jejunal glucose transport
| Autor: | Belharbi Krimi, Rim, Lettéron, Philippe, Chedid, Pia, Nazaret, Corinne, Ducroc, Robert, Marie, Jean-Claude |
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| Přispěvatelé: | Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Supported by grants from INSERM and Nestlé. |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Hormones
Ectopic MESH: Phosphorylation MESH: Rats MESH: Glucose Tolerance Test MESH: Intestinal Absorption MESH: Rats Wistar [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism MESH: Protein Kinase C MESH: Male MESH: Recombinant Proteins MESH: Glucose MESH: Mice Inbred C57BL MESH: Jejunum MESH: Sodium-Glucose Transporter 1 MESH: Biological Transport Active MESH: Intestinal Mucosa MESH: Sodium MESH: Glucose Transporter Type 2 MESH: Animals MESH: AMP-Activated Protein Kinases MESH: Mice |
| Zdroj: | Diabetes Diabetes, American Diabetes Association, 2009, 58 (9), pp.2032-8. ⟨10.2337/db08-1786⟩ |
| ISSN: | 0012-1797 |
| DOI: | 10.2337/db08-1786⟩ |
| Popis: | International audience; OBJECTIVE: An increased expression of RELM-beta (resistin-like molecule-beta), a gut-derived hormone, is observed in animal models of insulin resistance/obesity and intestinal inflammation. Intestinal sugar absorption is modulated by dietary environment and hormones/cytokines. The aim of this study was to investigate the effect of RELM-beta on intestinal glucose absorption. RESEARCH DESIGN AND METHODS: Oral glucose tolerance test was performed in mice and rats in the presence and the absence of RELM-beta. The RELM-beta action on glucose transport in rat jejunal sacs, everted rings, and mucosal strips was explored as well as downstream kinases modulating SGLT-1 and GLUT2 glucose transporters. RESULTS: Oral glucose tolerance test carried out in rodents showed that oral administration of RELM-beta increased glycemia. Studies in rat jejunal tissue indicated that mucosal RELM-beta promoted absorption of glucose from the gut lumen. RELM-beta had no effect on paracellular mannitol transport, suggesting a transporter-mediated transcellular mechanism. In studies with jejunal mucosa mounted in Ussing chamber, luminal RELM-beta inhibited SGLT-1 activity in line with a diminished SGLT-1 abundance in brush border membranes (BBMs). Further, the potentiating effect of RELM-beta on jejunal glucose uptake was associated with an increased abundance of GLUT2 at BBMs. The effects of RELM-beta were associated with an increased amount of protein kinase C betaII in BBMs and an increased phosphorylation of AMP-activated protein kinase (AMPK). CONCLUSIONS: The regulation of SGLT-1 and GLUT2 by RELM-beta expands the role of gut hormones in short-term AMPK/protein kinase C mediated control of energy balance. |
| Databáze: | OpenAIRE |
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