Bis‐Pyrano Prenyl Isoflavone Improves Glucose Homeostasis by Inhibiting Dipeptidyl Peptidase‐4 in Hyperglycemic Rats. Issue 1 (13th June 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 1(2017)
• Page Start: 92
• Page End: 103
• Publication Date: 2016-06-13
• Subjects: GLYCAEMIA -- DIABETES -- INCRETIN -- INSULIN -- CALCIUM -- ISOFLAVONES; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25614
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : 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 glycaemia in hyperglycemic rats. The acute 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. In addition, the in vitro isoflavone seems to inhibit dipeptidyl peptidase‐4 (DPP‐4) activity since the glucose tolerance was improved in the presence of the isoflavone as much as sitagliptin, inhibitor of DPP‐4. Furthermore, the isoflavone stimulates calcium influx in intestine colon and is mediated by voltage‐dependent calcium channels (VDCC), phospholipase C (PLC) activation, protein kinase C (PKC), and stored calcium contributing for GLP‐1 secretion. In conclusion, isoflavone seems to regulate glycaemia by acting mainly in a serum target, the DPP‐4 inhibitor. Additionally, the long‐term effect of isoflavone indicates a potential prevention on the late diabetes complication by diminishing protein glycation.