Honors Program


Date of this Version

Spring 3-24-2024

Document Type



Odom, H. 2024. Copper Deficiency Reduces Insulin Receptor and AKT Activation in House Hepatocytes. Undergraduate Honors Thesis. University of Nebraska - Lincoln.


Copyright Harper Odom 2024.


The liver is an essential organ for nutrient metabolism, and metabolic diseases, such as non-alcoholic fatty liver disease (NAFLD), affect its functions. NAFLD is characterized by steatosis, progressive liver damage, insulin resistance, and a deficiency of copper, an essential mineral nutrient. Proper metabolism of carbohydrates and lipids in the liver, in which insulin and copper play critical roles, is vital for maintaining energy balance in the body. Additionally, the liver removes insulin from the bloodstream, which controls the amount of insulin available to other tissues, such as skeletal muscle and fat cells. The insulin receptor, a protein on the cell surface, is crucial for insulin signaling and clearance. When insulin binds to the receptor, it triggers intracellular signaling events, including AKT protein kinase activation. This study investigated the relationship between the copper deficiency observed in NAFLD and insulin receptor-dependent signaling in the liver using immortalized and primary mouse hepatocytes. Insulin receptor phosphorylation and downstream AKT signaling activation following copper deficiency were assessed. The results showed that copper deficiency led to suppression of insulin-induced phosphorylation of its receptor and AKT and modification of the insulin receptor, which was reflected by its slower migration on a polyacrylamide gel. These findings suggest that adequate availability of copper is vital for proper insulin signaling in the liver.