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How Does The Undergo Muscle Insulin Resistance?

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Abstract

Insulin resistance is directly linked to insulin signaling in target tissues, including skeletal muscle. The purpose of this study is to determine if acylcarnitines undergo muscle insulin resistance. This research establishes a connection between incomplete β-oxidation of muscle fatty acids to development of insulin resistance and oxidative stress. C2C12 cells, primary mice muscle and human myotubes were isolated to test insulin, inflammatory and antioxidant response. Acylcarnitine treatment led to 20-30% decrease in insulin response in C2C12 cell cultures. Oxidative stress tripled by short and long chain acylcarnitines but reversed with antioxidant treatment. β-oxidation of fatty acids was significantly lower in insulin
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The relationship between β-oxidation of fatty acids and reactive oxygen species (ROS) production is inversely proportional under normal conditions (6). In type II diabetes, a large amount of reducing equivalents from β-oxidation enter the electron transport chain, diverting complex I where the core ROS production site resides (7,8). An obesity-related disorder such as diabetes causes inflammatory macrophages to invade white adipose tissue, causing inflammation and contributing to insulin resistance (9).
From recent research, it is hypothesized that insulin signaling in the cell can be influenced by acylcarnitines through a pro-inflammatory mechanism, causing insulin resistance (10). Although there is no direct correlation between insulin signaling and acylcarnitines, it is the aim of this study to determine the role of acylcarnitines in muscle insulin resistance. The behavior of acylcarnitines is a necessary component for connecting inefficient β-oxidation, oxidative, glucose response and inflammation.

Methods
For determination of oxidative stress and insulin response, C2C12 murine myoblasts, grown with approximately 90% confluence, were induced for differentiation and placed into myotubes. Primary muscle cells taken from mice were isolated for growth and differentiation. Human cells were collected from 10 subjects consisting of 5 lean and 5 overweight females.
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