Related Experiment Video
Updated: Jun 27, 2026

Hepatic Glucose Production, Ureagenesis, and Lipolysis Quantified using the Perfused Mouse Liver Model
Published on: October 6, 2023
Impact of insulin resistance on the progression of chronic liver diseases
Kosuke Kaji1, Hitoshi Yoshiji, Mitsuteru Kitade
1Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan.
Abstract:
Recent studies have revealed a close relationship between insulin resistance (IR) and the progression of chronic liver diseases, although relatively little is known regarding the possible mechanisms involved. The aim of this study was to elucidate the impact of IR on the development of liver fibrosis and hepatocarcinogenesis using obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Liver fibrosis development and glutathione-S-transferase placental form (GST-P)-positive pre-neoplastic lesions were both markedly accelerated in OLETF rats, being induced by pig serum and diethylnitrosamine (DEN), respectively. In the fibrosis experiment, alpha-smooth muscle actin-positive activated hepatic stellate cells (HSCs) also significantly increased in OLETF rats along with augmentation of the hepatic collagen content and transforming growth factor-beta1. Our in vitro study showed that both glucose and insulin stimulated the proliferation of activated HSCs, and the combination treatment exerted an additive effect. In the DEN model, neovascularization, which plays a pivotal role in hepatocarcinogenesis, was up-regulated in OLETF rats almost in parallel with pre-neoplastic lesion development and a potent angiogenic factor, vascular endothelial growth factor. High glucose and insulin also significantly augmented the in vitro neovascularization via extracellular signal-regulated kinase 1/2 phosphorylation. Similar to the effect on the activated HSCs, co-existence of both factors exerted a more potent effect than either single factor. In conclusion, these results indicated that the IR status directly accelerated liver fibrosis development and hepatocarcinogenesis at least partly through the stimulation of activated HSC proliferation and hepatic neovascularization, respectively, in the rat.
More Related Videos
08:41Novel In Vivo Micro-Computed Tomography Imaging Techniques for Assessing the Progression of Non-Alcoholic Fatty Liver Disease
Published on: March 24, 2023
08:13Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT)
Published on: January 7, 2018
Related Concept Videos
Type II Diabetes II: Pathophysiology
Chronic Pancreatitis II: Pathophysiology
Chronic Pancreatitis I: Introduction
Chronic Pancreatitis I: Introduction
Pancreatitis is the inflammation of the pancreas, which occurs when the immune system becomes active and causes swelling, pain, and disruptions in organ function. Pancreatitis can manifest as either an acute or chronic condition.
Acute pancreatitis arises suddenly and lasts for a brief duration, while chronic pancreatitis is a long-term affliction...
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test