title: SGLT1 activity in lung alveolar cells of diabetic rats modulates airway surface liquid glucose concentration and bacterial proliferation.
abstract: High glucose concentration in the airway surface liquid (ASL) is an important feature of diabetes that predisposes to respiratory infections. We investigated the role of alveolar epithelial SGLT1 activity on ASL glucose concentration and bacterial proliferation. Non-diabetic and diabetic rats were intranasally treated with saline, isoproterenol (to increase SGLT1 activity) or phlorizin (to decrease SGLT1 activity); 2 hours later, glucose concentration and bacterial proliferation (methicillin-resistant Sthaphylococcus aureus, MRSA and Pseudomonas aeruginosa, P. aeruginosa) were analyzed in bronchoalveolar lavage (BAL); and alveolar SGLT1 was analyzed by immunohistochemistry. BAL glucose concentration and bacterial proliferation increased in diabetic animals: isoproterenol stimulated SGLT1 migration to luminal membrane, and reduced (50%) the BAL glucose concentration; whereas phlorizin increased the BAL glucose concentration (100%). These regulations were accompanied by parallel changes of in vitro MRSA and P. aeruginosa proliferation in BAL (r = 0.9651 and r = 0.9613, respectively, Pearson correlation). The same regulations were observed in in vivo P. aeruginosa proliferation. In summary, the results indicate a relationship among SGLT1 activity, ASL glucose concentration and pulmonary bacterial proliferation. Besides, the study highlights that, in situations of pulmonary infection risk, such as in diabetic subjects, increased SGLT1 activity may prevent bacterial proliferation whereas decreased SGLT1 activity can exacerbate it.
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas, Alagoas, Brazil.|Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Tales Lyra
authors.initials: TL
authors.lastname: Oliveira
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas, Alagoas, Brazil.
authors.forename: Návylla
authors.initials: N
authors.lastname: Candeia-Medeiros
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas, Alagoas, Brazil.
authors.forename: Polliane M
authors.initials: PM
authors.lastname: Cavalcante-Araújo
authors.affiliation: Institute of Biological Sciences and Health, Federal University of Alagoas, Alagoas, Brazil.
authors.forename: Igor Santana
authors.initials: IS
authors.lastname: Melo
authors.affiliation: National Reference Center of Leprosy and Sanitary Dermatology, Federal University of Uberlandia, Minas Gerais, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: Fávaro-Pípi
authors.affiliation: Department of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Luciana Alves
authors.initials: LA
authors.lastname: Fátima
authors.affiliation: Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Antônio Augusto
authors.initials: AA
authors.lastname: Rocha
authors.affiliation: Institute of Genetics and Biochemistry, Federal University of Uberlandia, Minas Gerais, Brazil.|Department of Medical Microbiology and Immunology, University of California Davis, California, USA.
authors.forename: Luiz Ricardo
authors.initials: LR
authors.lastname: Goulart
authors.affiliation: Department of Physiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Ubiratan Fabres
authors.initials: UF
authors.lastname: Machado
authors.affiliation: Department of Physiology, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Ruy R
authors.initials: RR
authors.lastname: Campos
authors.affiliation: Department of Physiology, Institute of Biomedical Sciences, Federal University of Uberlandia, Minas Gerais, Brazil.
authors.forename: Robinson
authors.initials: R
authors.lastname: Sabino-Silva
mesh_terms: D000496:Alloxan; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000382:microbiology; D001993:Bronchodilator Agents / Q000494:pharmacology; D015169:Colony Count, Microbial; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D010695:Phlorhizin / Q000494:pharmacology; D018410:Pneumonia, Bacterial / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011552:Pseudomonas Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development; D051381:Rats; D017208:Rats, Wistar; D051269:Sodium-Glucose Transporter 1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D013203:Staphylococcal Infections / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D001993:Bronchodilator Agents; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D000496:Alloxan; D010695:Phlorhizin; D005947:Glucose; D007545:Isoproterenol