title: Protein malnutrition potentiates the amplifying pathway of insulin secretion in adult obese mice.
abstract: Pancreatic beta cell (β) dysfunction is an outcome of malnutrition. We assessed the role of the amplifying pathway (AMP PATH) in β cells in malnourished obese mice. C57Bl-6 mice were fed a control (C) or a low-protein diet (R). The groups were then fed a high-fat diet (CH and RH). AMP PATH contribution to insulin secretion was assessed upon incubating islets with diazoxide and KCl. CH and RH displayed increased glucose intolerance, insulin resistance and glucose-stimulated insulin secretion. Only RH showed a higher contribution of the AMP PATH. The mitochondrial membrane potential of RH was decreased, and ATP flux was unaltered. In RH islets, glutamate dehydrogenase (GDH) protein content and activity increased, and the AMP PATH contribution was reestablished when GDH was blunted. Thus, protein malnutrition induces mitochondrial dysfunction in β cells, leading to an increased contribution of the AMP PATH to insulin secretion through the enhancement of GDH content and activity.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Nayara Carvalho
authors.initials: NC
authors.lastname: Leite
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Flávia
authors.initials: F
authors.lastname: de Paula
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Patrícia Cristine
authors.initials: PC
authors.lastname: Borck
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Jean Franciesco
authors.initials: JF
authors.lastname: Vettorazzi
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Renato Chaves Souto
authors.initials: RC
authors.lastname: Branco
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Lubaczeuski
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Antonio Carlos
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Claudio Cesar
authors.initials: CC
authors.lastname: Zoppi
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, CEP: 13083-865, Brazil.
authors.forename: Everardo Magalhães
authors.initials: EM
authors.lastname: Carneiro
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D018149:Glucose Intolerance / Q000150:complications / Q000378:metabolism / Q000473:pathology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008928:Mitochondria / Q000378:metabolism; D011502:Protein-Energy Malnutrition / Q000150:complications / Q000378:metabolism* / Q000473:pathology
chemical_list: D007328:Insulin; D005969:Glutamate Dehydrogenase