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

Diabetologia. 2006 Oct;49(10):2437-48. doi: 10.1007/s00125-006-0373-6. Epub 2006 Aug 9.


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-beta 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.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / physiology
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cinnamomum zeylanicum*
  • Coumaric Acids / pharmacology*
  • Epididymis
  • Glucose / metabolism*
  • Glucose Tolerance Test
  • Glucose Transporter Type 4 / drug effects
  • Glucose Transporter Type 4 / metabolism*
  • Glycogen / biosynthesis
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Naphthalenes / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Transport / drug effects


  • Blood Glucose
  • Coumaric Acids
  • Glucose Transporter Type 4
  • Naphthalenes
  • Glycogen
  • Phosphatidylinositol 3-Kinases
  • Glucose