title: Incretinomimetic and Insulinomimetic Effect of (2E)-N'-(1'-Naphthyl)-3,4,5-Trimethoxybenzohydrazide for Glycemic Homeostasis.
abstract: To characterize the role and the mechanism of action of (2E)-N'-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide (BZD) on incretin secretion, glucose uptake in skeletal muscle and α-glucosidase activity on intestine, targets for glucose homeostasis. It was assayed on glucose tolerance test (GTT) to analyze GLP-1 secretion and the activity of DPP-4 enzyme in vitro. In skeletal muscle, mechanism of action on glucose uptake was carried out by in vitro experiments. The activity of intestinal disaccharidases was performed after in vivo and in vitro experiments. The compound improved the glucose tolerance around 30%, 25%, and 20% at 15, 30, and 60 min, respectively and potentiated the sitagliptin effect, an inhibitor of the enzyme that removes GLP-1, about 50, 45, and 54% at 15, 30, and 60 min, respectively. Additionally, BZD did not modify the activity of DPP-4 enzyme. The acute effect of BZD on glucose uptake is mediated by increasing GLUT4 expression (around 140%) and its translocation to the plasma membrane in soleus muscle. The genomic effect as well as GLUT4 translocation involve the activation of PI-3K and MAPK pathways and require the microtubules integrity to the complete stimulatory effect of this compound on glucose uptake. Beyond, BZD acts in an alternative target to ameliorate glycaemia, intestinal disaccharidases. In a whole, these data point an incretino- and insulinomimetic effect of the compound for glycemic control.
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Marisa Jádna Silva
authors.initials: MJ
authors.lastname: Frederico
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Campus Universitário, Bairro Trindade, CEP: 88040-900, Florianópolis, SC, Brazil.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mascarello
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Allisson Jhonatan Gomes
authors.initials: AJ
authors.lastname: Castro
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Da Luz
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Delsi
authors.initials: D
authors.lastname: Altenhofen
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Camila Pires
authors.initials: CP
authors.lastname: Mendes
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Campus Universitário, Bairro Trindade, CEP: 88040-900, Florianópolis, SC, Brazil.
authors.forename: Paulo Cesar
authors.initials: PC
authors.lastname: Leal
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Campus Universitário, Bairro Trindade, CEP: 88040-900, Florianópolis, SC, Brazil.
authors.forename: Rosendo Augusto
authors.initials: RA
authors.lastname: Yunes
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Campus Universitário, Bairro Trindade, CEP: 88040-900, Florianópolis, SC, Brazil.
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Nunes
authors.affiliation: Departamento de Bioquímica, Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Campus Universitário, Bairro Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, SC, Brazil.
authors.forename: Fátima Regina Mena Barreto
authors.initials: FR
authors.lastname: Silva
mesh_terms: D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D004186:Disaccharidases / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D006835:Hydrazones / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D054795:Incretins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007421:Intestine, Small / Q000187:drug effects / Q000201:enzymology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017208:Rats, Wistar
chemical_list: D000840:Anisoles; D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D006835:Hydrazones; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; C000604903:N-(1'-naphthyl)-3,4,5-trimethoxybenzohydrazide; D052216:Glucagon-Like Peptide 1; D019869:Phosphatidylinositol 3-Kinases; D004186:Disaccharidases; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: (2E)-N′-(1′-NAPHTHYL)-3,4,5-TRIMETHOXYBENZOHYDRAZIDE; DISACCHARIDASES; GLP-1; GLUCOSE UPTAKE; GLUT4