title: Bis-Pyrano Prenyl Isoflavone Improves Glucose Homeostasis by Inhibiting Dipeptidyl Peptidase-4 in Hyperglycemic Rats.
abstract: Isoflavones widely distributed in plants prevent diabetes. This study investigated the in vivo and in vitro effect of 3',4'-dihydroxy-6″,6″,6″',6″'-tetramethylbis(pyrano[2″,3″:5,6::2″',3″':7,8]isoflavone (bis-pyrano prenyl isoflavone) on glucose homeostasis in hyperglycemic rats. The ethyl acetate fraction from aerial parts of Polygala molluginifolia that contain isoflavones was assayed on glucose tolerance, on in vitro maltase activity and on protein glycation. The isoflavone bis-pyrano prenyl isolated from this fraction was investigated on glucose homeostasis. The in vivo action of the isoflavone exhibits an anti-hyperglycemic effect by improving glucose tolerance, augmenting the liver glycogen, inhibiting maltase activity, and stimulating glucagon-like peptide-1 (GLP-1) and insulin secretion. The in vitro isoflavone inhibits dipeptidyl peptidase-4 (DPP-4) activity since the glucose tolerance was improved in the presence of the isoflavone as much as sitagliptin, an inhibitor of DPP-4. However, the co-incubation with isoflavone and sitagliptin exhibited an additive anti-hyperglycemic action. The isoflavone increased the GLP-1 faster than the positive hyperglycemic group, which shows that the intestine is a potential target. Thus, to clarify the main site of action in which isoflavone improves glucose balance, the in vitro mechanism of action of this compound was tested in intestine using calcium influx as a trigger for the signal pathways for GLP-1 secretion. The isoflavone stimulates calcium influx in intestine and its mechanism involves voltage-dependent calcium channels, phospholipase C, protein kinase C, and stored calcium contributing for GLP-1 secretion. In conclusion, the isoflavone regulates glycaemia by acting mainly in a serum target, the DPP-4 inhibitor. Furthermore, the long-term effect of isoflavone prevents protein glycation. J. Cell. Biochem. 118: 92-103, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, Santa Catarina, Brazil.
authors.forename: Delsi
authors.initials: D
authors.lastname: Altenhofen
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, Santa Catarina, Brazil.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: da Luz
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, Santa Catarina, Brazil.
authors.forename: Marisa Jádna Silva
authors.initials: MJ
authors.lastname: Frederico
authors.affiliation: Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, CEP: 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Dalila
authors.initials: D
authors.lastname: Venzke
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, Santa Catarina, Brazil.
authors.forename: Mayara
authors.initials: M
authors.lastname: Brich
authors.affiliation: Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, CEP: 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Silvana
authors.initials: S
authors.lastname: Vigil
authors.affiliation: Departamento de Análises Clínicas, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, CEP: 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Tania Silvia
authors.initials: TS
authors.lastname: Fröde
authors.affiliation: Departamento de Ciências da Saúde, Centro de Ciências da Saúde, Universidade Regional Integrada do Alto Uruguai e da Missões, Campus Frederico Westphalen, Frederico Westphalen, Rio Grande do Sul, Brazil.
authors.forename: Carlos Eduardo Blanco
authors.initials: CE
authors.lastname: Linares
authors.affiliation: Departamento de Química, Centro de Ciências Físicas e Matemáticas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, CEP: 88040-900, Florianópolis, Santa Catarina, Brazil.
authors.forename: Moacir Geraldo
authors.initials: MG
authors.lastname: Pizzolatti
authors.affiliation: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Cx. Postal 5069, CEP: 88040-970, Florianópolis, Santa Catarina, Brazil.
authors.forename: Fátima Regina Mena Barreto
authors.initials: FR
authors.lastname: Silva
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007328:Insulin / Q000097:blood; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D031801:Polygala / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D007529:Isoflavones; D052216:Glucagon-Like Peptide 1; C000602659:DPP4 protein, rat; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: CALCIUM; DIABETES; GLYCAEMIA; INCRETIN; INSULIN; ISOFLAVONES