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

• Published in: Biochemical and biophysical research communications 2013-05, Vol.435 (2), p.165-170
• Main Authors: Takikawa, Masahito, Kurimoto, Yuta, Tsuda, Takanori
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Ca2+/calmodulin-dependent kinaseII; Calcium Signaling - drug effects; Calcium Signaling - physiology; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Cell Line; Curcumin; Curcumin - chemistry; Curcumin - pharmacology; Diabetes; Enteroendocrine Cells - drug effects; Enteroendocrine Cells - metabolism; Enzyme Activation - drug effects; Glucagon-Like Peptide 1 - secretion; Glucagon-like peptide-1; Intestinal L cells; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Mice; Secretion; Structure-Activity Relationship
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.04.092

•Curcumin significantly increases GLP-1 secretion in GLUTag cells.•One OCH3 moiety and β-diketone structure are essential for the GLP-1 secretion.•Curcumin-induced GLP-1 secretion involves the Ca2+-CaMKII pathway.•Curcumin-induced GLP-1 secretion is not regulated by the PKA, PKCζ, or ERK pathways. 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 Ca2+–Ca2+/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.