Brain glucagon-like peptide 1 signaling controls the onset of high-fat diet-induced insulin resistance and reduces energy expenditure

Autor: Eric Sabatier, Luc Pénicaud, Afifa Ait-Belgnaoui, Aurélie Waget, Alexandre Benani, Natacha Godet, Sophie Rastrelli, Rémy Burcelin, Marc Uldry, Claude Knauf, Cendrine Cabou, Philippe Valet, André Colom, Cédric Dray, Patrice D. Cani
Přispěvatelé: Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées- Institut Fédératif de Recherche Bio-médicale Institution (IFR150)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unit of Pharmacokinetics, Metabolism, Nutrition, and Toxicology (PMNT-73/69), Université Catholique de Louvain = Catholic University of Louvain (UCL), Neuro-Gastroentérologie et Nutrition (NGN), Institut National de la Recherche Agronomique (INRA)-Ecole supérieure d'agriculture de Purpan (ESAP), Métabolisme Plasticité et Mitochondrie [lié à l'ex IFR 31] (LMPM), IFR 31 Louis Bugnard (IFR 31), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Dana-Farber Cancer Institute [Boston], Simon, Marie Francoise, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole supérieure d'agriculture de Purpan (ESAP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Ecole supérieure d'agriculture de Purpan (ESAP)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Jazyk: angličtina
Rok vydání: 2008
Předmět:
Blood Glucose
Male
MESH: Signal Transduction
[SDV]Life Sciences [q-bio]
Messenger
Nitric Oxide Synthase Type II
Type 2 diabetes
Inbred C57BL
Proglucagon
MESH: Carbon Dioxide
Ion Channels
Mice
0302 clinical medicine
Endocrinology
Glucagon-Like Peptide 1
Hyperinsulinemia
Glycolysis
MESH: Animals
MESH: Oxygen Consumption
MESH: Peptide Fragments
0303 health sciences
MESH: Muscle
Skeletal
digestive
oral
and skin physiology
MESH: Energy Metabolism
MESH: Mitochondrial Proteins
Skeletal
Glucagon-like peptide-1
MESH: Motor Activity
MESH: Body Temperature Regulation
[SDV] Life Sciences [q-bio]
MESH: Insulin Resistance
MESH: Dietary Fats
MESH: Hyperinsulinism
Muscle
MESH: Nitric Oxide Synthase Type II
MESH: Physical Endurance
hormones
hormone substitutes
and hormone antagonists
Type 2
Body Temperature Regulation
Signal Transduction
MESH: Diabetes Mellitus
Type 2
medicine.medical_specialty
endocrine system
030209 endocrinology & metabolism
Biology
Motor Activity
Mitochondrial Proteins
03 medical and health sciences
Insulin resistance
Oxygen Consumption
MESH: Mice
Inbred C57BL
Internal medicine
Diabetes mellitus
Hyperinsulinism
Glucose Intolerance
medicine
Diabetes Mellitus
Animals
MESH: Mice
MESH: Glucose Intolerance
030304 developmental biology
MESH: RNA
Messenger
MESH: Glucagon-Like Peptide 1
Carbon Dioxide
medicine.disease
Dietary Fats
Peptide Fragments
MESH: Male
Basal (medicine)
MESH: Proglucagon
MESH: Ion Channels
MESH: Brain Stem
Physical Endurance
MESH: Blood Glucose
RNA
Insulin Resistance
Energy Metabolism
Thermogenesis
Brain Stem
Zdroj: Endocrinology
Endocrinology, 2008, 149 (10), pp.4768-77. ⟨10.1210/en.2008-0180⟩
Endocrinology, Endocrine Society, 2008, 149 (10), pp.4768-77. ⟨10.1210/en.2008-0180⟩
ISSN: 0013-7227
DOI: 10.1210/en.2008-0180⟩
Popis: International audience; Glucagon-like peptide-1 (GLP-1) is a peptide released by the intestine and the brain. We previously demonstrated that brain GLP-1 increases glucose-dependent hyperinsulinemia and insulin resistance. These two features are major characteristics of the onset of type 2 diabetes. Therefore, we investigated whether blocking brain GLP-1 signaling would prevent high-fat diet (HFD)-induced diabetes in the mouse. Our data show that a 1-month chronic blockage of brain GLP-1 signaling by exendin-9 (Ex9), totally prevented hyperinsulinemia and insulin resistance in HFD mice. Furthermore, food intake was dramatically increased, but body weight gain was unchanged, showing that brain GLP-1 controlled energy expenditure. Thermogenesis, glucose utilization, oxygen consumption, carbon dioxide production, muscle glycolytic respiratory index, UCP2 expression in muscle, and basal ambulatory activity were all increased by the exendin-9 treatment. Thus, we have demonstrated that in response to a HFD, brain GLP-1 signaling induces hyperinsulinemia and insulin resistance and decreases energy expenditure by reducing metabolic thermogenesis and ambulatory activity.
Databáze: OpenAIRE
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