title: Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.
abstract: In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2O2), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2O2and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2O2production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2O2(100 μM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.|Laboratory of Experimental Physiology, Department of Physiological Sciences, Federal University of Maranhão (UFMA), São Luís, Maranhão, Brazil.|Department of Physiology and Biophysiology, Institute of Biomedical Sciences, University of Sao Paulo (USP), São Paulo, Brazil.
authors.forename: Ana Paula G
authors.identifier: http://orcid.org/0000-0002-8018-0579
authors.initials: APG
authors.lastname: Cappelli
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Claudio C
authors.initials: CC
authors.lastname: Zoppi
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Leonardo R
authors.initials: LR
authors.lastname: Silveira
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Batista
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Flávia M
authors.initials: FM
authors.lastname: Paula
authors.forename: Priscilla M R
authors.initials: PMR
authors.lastname: da Silva
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.|Department of Physiologic Sciences, Center of Biologic Sciences, Federal University of Santa Catarina (UFSC), Florianopolis, Santa Catarina, Brazil.
authors.forename: Alex
authors.initials: A
authors.lastname: Rafacho
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Barbosa-Sampaio
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Boschero
authors.affiliation: Department of Structural and Functional Biology, Cellular Biology and Physiology and Biophysics, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Everardo M
authors.initials: EM
authors.lastname: Carneiro
mesh_terms: D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009752:Nutritional Status; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011502:Protein-Energy Malnutrition / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; C000606292:Sod1 protein, rat; D000072105:Superoxide Dismutase-1; D005978:Glutathione
keywords: antioxidant enzymes; insulin secretion; pancreatic islets; protein malnutrition; reactive oxygen species