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Title 

Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4

 

신남산의 나프탈렌메틸 에스

Authors 

W KimL Y KhilR ClarkSong Hae BokE E KimSangku LeeH S JunJ W Yoon

Publisher 

Springer Verlag (Germany)

Issue Date 

2006

Citation 

Diabetologia, vol. 49, no. 10, pp. 2437-2448

Keywords 

adipocyteglucose transporthydroxycinnamic acidsinsulin receptor signalphosphatidylinositol 3-kinaseantidiabetic agentdihydrocaffeic acidester derivativeglucoseglucose transporter 4

Abstract 

Aims/hypothesis: Cinnamon extracts have anti-diabetic effects. Phenolic acids, including hydrocinnamic acids, were identified as major components of cinnamon extracts. Against this background we sought to develop a new anti-diabetic compound using derivatives of hydroxycinnamic acids purified from cinnamon. Methods: We purified hydroxycinnamic acids from cinnamon, synthesised a series of derivatives, and screened them for glucose transport activity in vitro. We then selected the compound with the highest glucose transport activity in epididymal adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose-lowering activity in vivo, and studied the mechanisms involved. Results: A naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the highest glucose transport activity in vitro. Treatment of streptozotocin-induced diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased blood glucose levels to near normoglycaemia. Further studies revealed that DHH105 increased the maximum speed of glucose transport and the translocation of glucose transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-β subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in vivo. This resulted in the activation of phosphatidylinositol 3-kinase and Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma membrane. Conclusions/interpretation: We conclude that DHH105 lowers blood glucose levels through the enhancement of glucose transport, mediated by an increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a new anti-diabetic drug.

ISSN 

0012-186X

Link 

http://dx.doi.org/10.1007/s00125-006-0373-6

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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