Curcumin stimulates glucagon-like peptide-1 secretion in GLUTag cells via Ca2+/calmodulin-dependent kinase II activation

Biochem Biophys Res Commun. 2013 May 31;435(2):165-70. doi: 10.1016/j.bbrc.2013.04.092. Epub 2013 May 6.


Glucagon-like peptide-1 (GLP-1) is a hormone secreted from enteroendocrine L-cells. Enhancing GLP-1 action is an important target for prevention and treatment of type 2 diabetes. Several approaches (GLP-1 analogs, dipeptidyl peptidase IV inhibitors) are being used to develop therapeutic agents using GLP-1 action for the treatment of diabetes. However, an alternative approach is to increase endogenous GLP-1 secretion through modulation of the secretory mechanism in intestinal L cells by pharmaceutical agents or dietary ingredients. In the present study, we demonstrate that curcumin, a yellow pigment isolated from the rhizomes of Curcuma longa L, significantly increases GLP-1 secretion in GLUTag cells, and we clarified the structure-activity relationship using curcumin derivatives. Also, concerning the secretory mechanism, the significant increase in GLP-1 secretion by curcumin involved the Ca(2+)-Ca(2+)/calmodulin-dependent kinase II pathway, and was independent of extracellular signal-regulated kinase, PKC, and the cAMP/PKA-related pathway. These findings provide a molecular mechanism for GLP-1 secretion mediated by foods or drugs, and demonstrate a novel biological function of curcumin in regards to GLP-1 secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cell Line
  • Curcumin / chemistry*
  • Curcumin / pharmacology*
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Enzyme Activation / drug effects
  • Glucagon-Like Peptide 1 / metabolism*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Structure-Activity Relationship


  • Anti-Inflammatory Agents, Non-Steroidal
  • Glucagon-Like Peptide 1
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Curcumin