Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms

• Published in: Food chemistry 2012-12, Vol.135 (4), p.2350-2358
• Main Authors: Kang, Changkeun, Lee, Hyunkyoung, Jung, Eun-Sun, Seyedian, Ramin, Jo, MiNa, Kim, Jehein, Kim, Jong-Shu, Kim, Euikyung
• Format: Article
• Language: English
• Subjects: acetyl-CoA carboxylase; action potentials; AMP-activated protein kinase; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Aroma and flavouring agent industries; Biological and medical sciences; Biological Transport - drug effects; Cell Line; Crocus - chemistry; Crocus sativus; Diabetes Mellitus - genetics; Diabetes Mellitus - metabolism; Food industries; Fundamental and applied biological sciences. Psychology; glucose; Glucose - metabolism; Glucose Transporter Type 4 - genetics; Glucose Transporter Type 4 - metabolism; Glucose uptake; Humans; Insulin Resistance; Insulin sensitivity; MAP Kinase Signaling System - drug effects; mechanism of action; metabolism; Mice; mitogen-activated protein kinase; Muscle Cells - drug effects; Muscle Cells - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; myocytes; phosphatidylinositol 3-kinase; Plant Extracts - pharmacology; Saffron; skeletal muscle; Skeletal muscle cells; Up-Regulation - drug effects
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2012.06.092

► AMP-activated protein kinase (AMPK) has a key role in glucose metabolism of muscle. ► The activation of AMPK leads to GLUT4 translocation and glucose uptake in muscle. ► Saffron treatment stimulates glucose uptake via AMPK/ACC and MAPKs pathways. ► Saffron and insulin have a synergistic effect on glucose metabolism in muscle cells. Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C2C12 skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients.