MON-593 Hepatic PKCε Heterozygosity Does Not Improve Skeletal Muscle Insulin Resistance in Male Mice on High Fructose Diets

Abstract Disclosure: S. Muhammad: None. S. Andrisse: None. M. Rahman: None. Protein kinase C epsilon (PKCε) in the liver has been implicated as a key regulator of diet- induced insulin resistance but its role in peripheral tissues, such as skeletal muscle, remains unclear. This study highlights the role of hepatic PKCε in regulating skeletal muscle insulin sensitivity as measured by the AKT signaling pathway in response to high fructose diets. Male PKCε-heterozygous (PKCε-het) mice were fed either a high fructose or control diet for three months (Research Diets Inc, RDI). AKT protein and mRNA levels were analyzed under basal or insulin-stimulated conditions using Western Blot Analysis and qPCR, respectively. PKCe-Het mice on a control diet exhibited normal insulin sensitivity, while PKCe-Het mice on a high fructose diet displayed lowered p-AKT protein expression, suggesting skeletal muscle insulin resistance. These findings demonstrate that hepatic PKCε may not significantly regulate insulin sensitivity in skeletal muscle. Other data in our lab showed that PKCε-het was protective against HFrD-induced hepatic insulin resistance, despite a high fructose diet impairing insulin signaling in skeletal muscle. Targeting hepatic PKCε could be useful in developing therapies for conditions caused by diet-induced insulin resistance, such as Type 2 Diabetes and PCOS. Presentation: Monday, July 14, 2025