Premium
Bis‐Pyrano Prenyl Isoflavone Improves Glucose Homeostasis by Inhibiting Dipeptidyl Peptidase‐4 in Hyperglycemic Rats
Author(s) -
Altenhofen Delsi,
da Luz Gabrielle,
Frederico Marisa Jádna Silva,
Venzke Dalila,
Brich Mayara,
Vigil Silvana,
Fröde Tania Silvia,
Linares Carlos Eduardo Blanco,
Pizzolatti Moacir Geraldo,
Silva Fátima Regina Mena Barreto
Publication year - 2017
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.25614
Subject(s) - glucose homeostasis , isoflavones , chemistry , medicine , endocrinology , biochemistry , insulin , biology , insulin resistance
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.