The IDE Knockout SK-HEP-1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population of the human liver adenocarcinoma cell line SK-HEP-1, with targeted disruption of the IDE gene. This heterogeneous pool provides a robust loss-of-function model for studying IDE-mediated proteolysis of insulin, amyloid-beta, and other substrates. The polyclonal format ensures population-level diversity, minimizing clonal artifacts and enhancing reproducibility in downstream assays.
SK-HEP-1 is an ascites-derived human liver adenocarcinoma cell line that retains epithelial morphology and robust insulin signaling capacity, making it a valuable host for metabolic research. Originally isolated from a patient with liver adenocarcinoma, this cell line is frequently employed in studies of hepatic insulin clearance, drug metabolism, and hepatocellular carcinoma. Its amenability to CRISPR/Cas9 editing and high-throughput protocols facilitates detailed mechanistic and pharmacological investigations in a liver-relevant context.
IDE encodes a zinc metallopeptidase that degrades insulin, glucagon, amyloid-beta, amylin, and somatostatin. It is regulated by insulin and PPAR-gamma, and its activity modulates insulin receptor signaling and amyloid-beta clearance. By cleaving insulin, IDE influences downstream kinases such as AKT and ERK, affecting glucose uptake and metabolic homeostasis. IDE requires zinc as a cofactor and directly interacts with its peptide substrates. Knockout of IDE eliminates this proteolytic activity, leading to substrate accumulation and altered signaling, positioning IDE at the nexus of metabolic and neurodegenerative pathway regulation.
In the SK-HEP-1 hepatic background, IDE knockout disrupts the primary route of insulin degradation, causing prolonged insulin receptor activation and enhanced downstream signaling. This model is ideal for studying hepatic insulin clearance and its role in type 2 diabetes and metabolic syndrome. Additionally, the liver??s role in peripheral amyloid-beta clearance makes these cells useful for investigating hepatic contributions to Alzheimer??s disease. The loss of IDE in this liver adenocarcinoma line also permits exploration of IDE??s potential function in cancer cell metabolism and growth.
Typical assays include insulin degradation kinetics, amyloid-beta clearance assays, glucose uptake quantification, and phospho-AKT/ERK signaling analysis by western blotting. This polyclonal knockout population supports high-throughput screening of IDE inhibitors or activators and is relevant for diabetes, Alzheimer??s, and metabolic syndrome research. The cells also serve as a platform for studying peptide hormone degradation and its impact on cellular metabolism. For further details or custom inquiries, please contact Ascent Research.
