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Integrative Health

This Is The Often Overlooked Cause Of Insulin Resistance (Nope, Not Sugar!)

Author: Ava Durgin

March 22, 2026

Assistant Health Editor

By Ava Durgin

Assistant Health Editor

Ava Durgin is the former Assistant Health Editor at mindbodygreen. She holds a B.A. in Global Health and Psychology from Duke University.

Image by Cate Shanahan x mbg creative

March 22, 2026

When most people think about insulin resistance, sugar is usually the first thing that comes to mind. And while excessive sugar consumption can certainly play a role, emerging research—and experts like Cate Shanahan, M.D.—suggests that oxidative stress may be a major, and often overlooked, driver of insulin resistance.

On the mindbodygreen podcast, Shanahan shared her perspective on how oxidative stress, fueled in part by industrial seed oils, can disrupt metabolism and contribute to insulin resistance—a condition that affects one in three adults in the United States and significantly increases the risk of Type 2 diabetes and other chronic diseases.

Here's the science behind oxidative stress, how it impacts insulin signaling, and why cutting back on certain oils may be a smart step for your metabolic health.

What is oxidative stress & why does it matter?

Oxidative stress occurs when there's an imbalance between reactive oxygen species (ROS), which are unstable molecules produced during normal metabolism, and the body's ability to neutralize them with antioxidants. While small amounts of ROS are essential for cellular signaling, excessive levels can cause widespread damage to cells, tissues, and critical metabolic pathways.

Research has shown that oxidative stress plays a direct role in insulin resistance by interfering with the insulin receptor signaling pathway—the very process that allows your body to move glucose from the bloodstream into your cells.

According to Shanahan, one of the primary culprits driving oxidative stress is the modern diet, particularly the widespread use of refined vegetable oils like soybean, corn, and canola oil.

How oxidative stress disrupts insulin signaling

To understand how oxidative stress causes insulin resistance, it's helpful to break down the insulin receptor signaling pathway. This is the process that regulates glucose uptake in your body.

When you eat carbohydrates, your pancreas releases insulin, which binds to insulin receptors on the surface of muscle and fat cells. This triggers a cascade of signals that ultimately allows GLUT4, a glucose transporter protein, to move glucose from your blood into your cells, providing energy and maintaining healthy blood sugar levels.

But when oxidative stress is elevated, this system breaks down.

Research shows that reactive oxygen species (ROS) can disrupt this process in several ways:

- Inhibiting GLUT4 transporters: ROS reduce the expression of GLUT4, meaning glucose cannot effectively enter your cells, leading to elevated blood sugar levels.

- Mitochondrial dysfunction: Increased ROS production in mitochondria (your cells' energy factories) further amplifies oxidative stress, creating a vicious cycle that promotes insulin resistance.

- Inflammation activation: ROS triggers inflammatory pathways like NF-κB and JNK, which interfere with insulin receptor function and reduce insulin sensitivity.

This cascade ultimately leads to hyperinsulinemia—elevated insulin levels—as the pancreas works overtime to compensate for the body's reduced insulin sensitivity. Over time, this chronic overstimulation can exhaust the pancreas, increasing the risk of Type 2 diabetes.

The role of seed oils in oxidative stress

So, where do seed oils fit into this picture? According to Shanahan, the answer lies in their high polyunsaturated fat (PUFA) content, specifically omega-6 fatty acids like linoleic acid.

While omega-6 fats are essential in small amounts, excessive consumption, especially in their oxidized form, can significantly increase oxidative stress. Here's why:

- Highly unstable under heat: When exposed to high temperatures (such as during frying), the PUFAs in seed oils break down and generate harmful by-products called oxidized linoleic acid metabolites. These compounds promote inflammation and damage cellular structures.

- Stored in body fat: Unlike sugar, which is burned quickly for energy, PUFAs from seed oils are incorporated into your cell membranes and fat stores, where they can continue to promote oxidative damage over time.

- Mitochondrial stress: Research suggests that an increased PUFA load impairs mitochondrial function, leading to more ROS production, a key driver of insulin resistance.

In fact, research suggests that oxidized omega-6 fats may be a significant driver of coronary heart disease and other metabolic disorders.

Why obesity increases oxidative stress & insulin resistance

Excess body fat, particularly visceral fat, is a major contributor to oxidative stress. As fat cells grow, they release free fatty