Related Experiment Video
Updated: Dec 29, 2025

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
Oleoylethanolamide Increases Glycogen Synthesis and Inhibits Hepatic Gluconeogenesis via the LKB1/AMPK Pathway in
Tong Ren1, Ang Ma1, Rengong Zhuo1
1Xiamen Key Laboratory of Chiral Drugs, School of Medicine, Xiamen University, Xiamen, China (T.R., A.M., R.Z., H.Z., L.P., X.J., L.Y.) and Department of Cardiology, Fujian Medical University Union Hospital, Fujian Institute of Coronary Artery Disease, Fujian Heart Medical Center, Fuzhou, China (E.Y.).
Abstract:
Oleoylethanolamide (OEA) is an endogenous peroxisome proliferator-activated receptor α (PPARα) agonist that acts on the peripheral control of energy metabolism. However, its therapeutic potential and related mechanisms in hepatic glucose metabolism under type 2 diabetes mellitus (T2DM) are not clear. Here, OEA treatment markedly improved glucose homeostasis in a PPARα-independent manner. OEA efficiently promoted glycogen synthesis and suppressed gluconeogenesis in mouse primary hepatocytes and liver tissue. OEA enhanced hepatic glycogen synthesis and inhibited gluconeogenesis via liver kinase B1 (LKB1)/5' AMP-activated protein kinase (AMPK) signaling pathways. PPARα was not involved in the roles of OEA in the LKB1/AMPK pathways. We found that OEA exerts its antidiabetic effect by increasing glycogenesis and decreasing gluconeogenesis via the LKB1/AMPK pathway. The ability of OEA to control hepatic LKB1/AMPK pathways may serve as a novel therapeutic approach for the treatment of T2DM. SIGNIFICANCE STATEMENT: Oleoylethanolamide (OEA) exerted a potent antihyperglycemic effect in a peroxisome proliferator-activated receptor α-independent manner. OEA played an antihyperglycemic role primarily via regulation of hepatic glycogen synthesis and gluconeogenesis. The main molecular mechanism of OEA in regulating liver glycometabolism is activating the liver kinase B1/5' AMP-activated protein kinase signaling pathways.
Related Concept Videos
Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
cAMP-dependent Protein Kinase Pathways
Dipeptidyl Peptidase 4 Inhibitors
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors
Acarbose and miglitol are...
Hormones Regulating Blood Glucose
In addition to accelerating glucose uptake and utilization, insulin has...
Oral Hypoglycemic Agents: Biguanides and Glitazones

