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Incretinomimetic and Insulinomimetic Effect of ( 2E )‐N′‐(1′‐Naphthyl)‐3,4,5‐Trimethoxybenzohydrazide for Glycemic Homeostasis
Author(s) -
Silva Frederico Marisa Jádna,
Mascarello Alessandra,
Castro Allisson Jhonatan Gomes,
Da Luz Gabrielle,
Altenhofen Delsi,
Mendes Camila Pires,
Leal Paulo Cesar,
Yunes Rosendo Augusto,
Nunes Ricardo José,
Silva Fátima Regina Mena Barreto
Publication year - 2016
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25403
Subject(s) - glucose homeostasis , medicine , endocrinology , glucose transporter , chemistry , incretin , disaccharidase , glucose uptake , in vivo , homeostasis , glut4 , enzyme , insulin , biochemistry , biology , type 2 diabetes , insulin resistance , diabetes mellitus , microbiology and biotechnology
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. J. Cell. Biochem. 117: 1199–1209, 2016. © 2015 Wiley Periodicals, Inc.