Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells.
Curcumin, the bioactive component of curry spice turmeric, and its related structures possess potent anti-oxidant and anti-inflammatory properties. Several lines of evidence suggest that curcumin may play a beneficial role in animal models of diabetes, both by lowering blood glucose levels and by ameliorating the long-term complications of diabetes. However, current understanding of the mechanism of curcumin action is rudimentary and is limited to its anti-oxidant and anti-inflammatory effects. In this study we examine potential anti-diabetic mechanisms of curcumin, curcumin C3 complex), and tetrahydrocurcuminoids (THC). Curcuminoids did not exert a direct effect on receptor tyrosine kinase activity, 2-deoxy glucose uptake in L6-GLUT4myc cells, or intestinal glucose metabolism measured by DPP4/alpha-glucosidase inhibitory activity. We demonstrate that curcuminoids effectively suppressed dexamethasone-induced phosphoenol pyruvate carboxy kinase (PEPCK) and glucose6-phosphatase (G6Pase) in H4IIE rat hepatoma and Hep3B human hepatoma cells. Furthermore, curcuminoids increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target acetyl-CoA carboxylase (ACC) in H4IIE and Hep3B cells with 400 times (curcumin) to 100,000 times (THC) the potency of metformin. These results suggest that AMPK mediated suppression of hepatic gluconeogenesis may be a potential mechanism mediating glucose-lowering effects of curcuminoids.
Kim
Teayoun
T
Department of Nutrition and Food Science, Boshell Diabetes and Metabolic Diseases, Research Program, Auburn University, Auburn, AL 36849, USA.
Davis
Jessica
J
Zhang
Albert J
AJ
He
Xiaoming
X
Mathews
Suresh T
ST
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects* / Q000235:genetics; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000819:agonists; D000520:alpha-Glucosidases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D011972:Receptor, Insulin; D055372:AMP-Activated Protein Kinases; D000520:alpha-Glucosidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C520105:ACACB protein, human; D000103:Acetyl-CoA Carboxylase; D003474:Curcumin