Case Study: Pathogenesis of Insulin Resistance and Diet Analysis

This assignment provides a detailed analysis of insulin resistance, integrating signaling pathways and substrate flux, based on a review of the JCI article by Samuel and Shulman. It explores how chronic energy surplus and ectopic lipid accumulation in the liver and skeletal muscle impair insulin signaling, leading to reduced muscle glucose uptake and decreased hepatic glycogen synthesis. The study highlights the role of macrophage infiltration into white adipose tissue (WAT), leading to increased lipolysis and subsequent hepatic triglyceride synthesis and hyperlipidemia. Furthermore, it discusses how insulin resistance in muscle precedes liver insulin resistance, diverting ingested glucose to the liver, resulting in increased hepatic de novo lipogenesis and hyperlipidemia. The analysis also covers the impact of insulin on hepatic glucose metabolism, both directly and indirectly through adipose tissue, and suggests therapies targeting ectopic lipid storage and macrophage-induced WAT lipolysis to reverse the root causes of type 2 diabetes. This document is available on Desklib, a platform offering a range of study tools and solved assignments for students.