Insulinotropic agent ID-1101 (4-hydroxyisoleucine) activates insulin signaling in rat
| Autor: | Christine Rouault, René Gross, Michel Derouet, Céline Cruciani-Guglielmacci, Gérard Reach, M. Manteghetti, Mohammed Taouis, Pierre Petit, Gérard Ribes, Vincent Breil, Christophe Broca, Salwa W. Rizkalla, Bernard Pau, Alain Ktorza |
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| Přispěvatelé: | Unité de Recherches Avicoles (URA), Institut National de la Recherche Agronomique (INRA), Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génie Biomédical et Diabète Sucré, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physiopathologie de la nutrition (LPN), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre de pharmacologie et innovation dans le diabète (CPID), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), Maladies Métaboliques, Institut de Rechercjhes SERVIER, Laboratoire de Neuroendocrinologie Moléculaire de la Prise Alimentaire, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d’études d’Agents Pathogènes et Biotechologies pour la Santé (CPBS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), ProdInra, Migration, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1) |
| Rok vydání: | 2004 |
| Předmět: |
insulinémie
MESH: Signal Transduction Male Sucrose Physiology [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology [SDV]Life Sciences [q-bio] Endocrinology Diabetes and Metabolism medicine.medical_treatment MESH: Rats Zucker métabolisme nutritionnel MESH: Rats Sprague-Dawley MESH: Isoleucine rattus rattus MESH: Glucose Clamp Technique Rats Sprague-Dawley Phosphatidylinositol 3-Kinases 0302 clinical medicine MESH: Diabetes Mellitus Experimental MESH: Obesity Insulin MESH: Animals ComputingMilieux_MISCELLANEOUS Euglycemic hyperinsulinemic clamp chemistry.chemical_classification MESH: Muscle Skeletal 0303 health sciences [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior biology [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences Lipids Amino acid [SDV] Life Sciences [q-bio] MESH: Glucose obésité MESH: Insulin Resistance nutrition Liver Biochemistry MESH: Hyperinsulinism Signal transduction diabète Signal Transduction Niacinamide MESH: Enzyme Activation medicine.medical_specialty RAT 4-HYDROXYISOLEUCINE MESH: Rats 030209 endocrinology & metabolism MESH: Insulin [INFO] Computer Science [cs] Diabetes Mellitus Experimental 03 medical and health sciences Insulin resistance MESH: Diet Hyperinsulinism Physiology (medical) Internal medicine medicine Animals [INFO]Computer Science [cs] Obesity Isoleucine Muscle Skeletal résistance à l'insuline insuline Pancreatic hormone 030304 developmental biology MESH: Sucrose medicine.disease MESH: Lipids MESH: Male Diet Rats Rats Zucker Enzyme Activation Insulin receptor Glucose Enzyme Endocrinology chemistry MESH: Phosphatidylinositol 3-Kinases Glucose Clamp Technique biology.protein Insulin Resistance MESH: Niacinamide MESH: Liver |
| Zdroj: | AJP-Endocrinology and Metabolism AJP-Endocrinology and Metabolism, American Physiological Society, 2004, 287, pp.E463-E471 AJP-Endocrinology and Metabolism, American Physiological Society, 2004, 287 (3), pp.E463-E471. ⟨10.1152/ajpendo.00163.2003⟩ AJP-Endocrinology and Metabolism, 2004, 287 (3), pp.E463-E471. ⟨10.1152/ajpendo.00163.2003⟩ American Journal of Physiology. Endocrinology and Metabolism (287), E463-E471. (2004) |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00163.2003 |
| Popis: | International audience; ID-1101 (4-hydroxyisoleucine), an amino acid extracted from fenugreek seeds, exhibits an interesting glucose-dependent insulin-stimulating activity. The present study was undertaken to investigate a possible extrapancreatic effect of ID-1101 on insulin signaling and action besides its previously described insulinotropic action. Insulin-sensitizing effects of ID-1101 were investigated in rat in vivo by three different approaches: 1) using euglycemic hyperinsulinemic clamps in two different rat models of insulin resistance, i.e., Zucker fa/fa rats and rats fed a sucrose-lipid diet; 2) measuring liver and muscle phosphatidylinositol (PI) 3-kinase activity after an acute injection of ID-1101 in normal and insulin-resistant diabetic rats; and 3) after chronic treatment in two rat models of insulin resistance. Euglycemic hyperinsulinemic clamp experiments revealed that ID-1101 can improve insulin resistance through an increase of peripheral glucose utilization rate in sucrose-lipid-fed rats and by decreasing hepatic glucose production in Zucker fa/fa rats. Moreover, we demonstrated that a single injection of ID-1101 activates the PI 3-kinase activity in liver and muscle from normal rats but also in muscle from diabetic rats. Finally, chronic ID-1101 treatment significantly reduced insulinemia in type 2 diabetic rats and reduced the progression of hyperinsulinemia in insulin-resistant obese Zucker fa/fa rats. These findings clearly demonstrate that ID-1101 can reduce insulin resistance through activation of the early steps of insulin signaling in peripheral tissues and in liver. In summary, ID-1101, besides its insulinotropic effect, directly improves insulin sensitivity, making it a potentially very valuable therapeutic agent for diabetes treatment. |
| Databáze: | OpenAIRE |
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