title: Neuregulin 1 Improves Glucose Tolerance in db/db Mice.
abstract: In vitro experiments using rodent skeletal muscle cells suggest that neuregulin 1 (NRG1) is involved in glucose metabolism regulation, although no study has evaluated the role of NRG1 in systemic glucose homeostasis. The purpose of this study was to investigate the effect of chronic and acute NRG1 treatment on glucose homeostasis in db/db mice. To this aim, glucose tolerance tests were performed in 8-week-old male db/db mice after treatment with NRG1 (50μg.kg-1) or saline 3 times per week for 8 weeks. In other experiments, glucose tolerance and pyruvate tolerance tests were performed in db/db mice 15 minutes after a single NRG1 (50μg.kg-1) or saline injection. Liver, adipose tissue, hypothalamus and skeletal muscle were also collected 30 minutes after acute NRG1 (50μg.kg-1) or saline treatment, and the phosphorylation status of the ERBB receptors, AKT (on Ser473) and FOXO1 (on Ser256) was assessed by western blotting. Chronic treatment (8 weeks) with NRG1 improved glucose tolerance in db/db mice. Acute treatment also lowered glycemia and insulinemia during glucose or pyruvate tolerance tests. NRG1 acute injection induced activation of ERBB3 receptors and phosphorylation of AKT and FOXO1 only in liver. Altogether, this study shows that acute and chronic NRG1 treatments improve glucose tolerance in db/db mice. This effect could be mediated through inhibition of hepatic gluconeogenesis.
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Gaël
authors.initials: G
authors.lastname: Ennequin
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boisseau
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Kevin
authors.initials: K
authors.lastname: Caillaud
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Vivien
authors.initials: V
authors.lastname: Chavanelle
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Etienne
authors.affiliation: Zensun Sci & Tech Ltd., Shanghai, China.
authors.forename: Xinyan
authors.initials: X
authors.lastname: Li
authors.affiliation: Université Clermont Auvergne, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l'Exercice en Conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171, Aubière Cedex, France; CRNH-Auvergne, Clermont-Ferrand, F-63001, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sirvent
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005943:Gluconeogenesis / Q000502:physiology; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D020890:Neuregulin-1 / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D007328:Insulin; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt