Hepatic insulin resistance is a key contributor to metabolic syndrome, leading to conditions like type 2 diabetes, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Ace Therapeutics offers high-quality in vitro hepatocyte insulin resistance models to support the preclinical development of novel insulin-sensitizing therapeutics.
Insulin resistance (IR) represents a condition where the body's response to insulin is diminished, leading to reduced effectiveness in regulating glucose levels. Predominantly affecting the liver and peripheral tissues, IR significantly contributes to the onset of type 2 diabetes. Given the challenges and limitations of conducting research directly on human subjects, in vitro cellular assays play a crucial role in studying IR. Liver cells are particularly valuable in these studies due to their abundance, ability to regenerate, and ease of access, making them a preferred choice for modeling insulin resistance and exploring related metabolic processes.
Fig. 1. The insulin signaling pathway in hepatocytes (HepG2 cell lines). (Yudhani R D, et al., 2023)
At Ace Therapeutics, most of the hepatocyte models we currently use are derived from animal primary hepatocytes and human hepatocellular carcinoma cells (HepG2), which are derived from human hepato-embryonic tumor cells and are phenotypically very similar to hepatocytes.
| Model Types | Advantages | Applications |
| Primary Rat Hepatocyte Model | Easy to artificially control culture conditions Simultaneously obtains a large number of homogeneous samples Functional and cellular differentiation status largely preserved |
Enzyme induction and inhibition studies Research on the pathogenesis of insulin resistance Drug screening |
| HepG2 Cell Model | Exhibits specific hepatocyte morphology Expression of hepatocyte-specific markers Easy to culture in vitro Simple and reproducible |
Research on insulin signaling or the molecular mechanisms of metabolic processes Research on the mechanism of action of hypoglycemic substances |
To mimic the complex pathophysiology of hepatic IR, we employ a multifaceted approach to induce insulin-resistant phenotypes in their hepatocyte cultures. This includes:
Nutrient Overload: Exposing the hepatocytes to high glucose, free fatty acids, or a combination of both to recapitulate the metabolic stress associated with type 2 diabetes.
Inflammatory Stimuli: Challenging the cells with pro-inflammatory cytokines, such as TNF-α or IL-6, to investigate the interplay between inflammation and hepatic IR.
Genetic Manipulations: Silencing or overexpressing key molecules involved in insulin signaling or glucose/lipid metabolism to dissect the specific molecular mechanisms underlying IR in the liver.
By offering a physiologically relevant in vitro system to study the complex mechanisms of hepatic insulin resistance, our company's services enable clients to:
For more information on how our services can be customized to meet your exact needs, please contact us. Work with us and leverage our specialized cell models and innovative analytical services to accelerate your diabetes research.
Ace Therapeutics has a team of experts in the field of endocrine and metabolic research, aiming to provide innovative preclinical contract research solutions to cope with diabetes and its complications. We provide customized solutions and technical support, enabling the transformation of promising concepts into innovative treatments, thus accelerating the drug development process of diabetes.
