Prolonged Exposure to Insulin Might Cause Epigenetic Alteration Leading to Insulin Resistance

Jan 26, 2025
Ben Bikman
Prolonged Exposure to Insulin Might Cause Epigenetic Alteration Leading to Insulin Resistance
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(The recording above is from Dr. Bikman’s Research Reviews Podcast. You can receive these reviews each week, via email, by becoming an Insider.)


Dr. Ben Bikman, a professor of cell biology and metabolic scientist, recently highlighted a groundbreaking study titled “Prolonged Exposure to Insulin Might Cause Epigenetic Alterations Leading to Insulin Resistance.” Published in FEBS Open Bio in 2024, this research, conducted by scientists in India, sheds light on a profound question: could prolonged elevated insulin—independent of blood sugar—be a driving force behind insulin resistance?

What Is Insulin’s Role in the Body?

To answer that question, it’s important to revisit what insulin does. Insulin is a vital hormone that regulates glucose homeostasis, ensuring glucose is transported into cells for energy storage and use. Importantly, insulin is present in the bloodstream at all times, not just when food is consumed. However, in today’s modern environment of frequent meals, carbohydrate-rich diets, and constant snacking, many people live in a near-constant state of elevated insulin. Over time, this persistent elevation can have serious consequences.

How Prolonged Insulin Exposure Causes Resistance

The study discussed used cellular and animal models to explore this phenomenon. The researchers demonstrated that prolonged exposure to insulin—even in the absence of high blood sugar—can induce insulin resistance. Cells exposed to insulin for extended periods under low-glucose conditions showed impaired glucose transporter activity and reduced signaling in key metabolic pathways. Even more fascinating, the insulin resistance persisted even after the cells were returned to normal conditions, suggesting that epigenetic changes—alterations in gene expression—were at play. Specifically, the researchers observed increased methylation of histones, proteins that help package DNA, which influenced the expression of genes involved in insulin signaling.

Key Findings from Animal Models

These findings were further confirmed in a mouse model. When fasting mice were administered low doses of insulin, mimicking prolonged hyperinsulinemia, the animals developed insulin resistance, even without exposure to high blood sugar. Over time, their fasting glucose levels rose, and they showed early signs of metabolic dysfunction, such as enlarged pancreatic islets and subtle changes in adipose tissue—hallmarks of type 2 diabetes.

Implications for Metabolic Health

Why is this important? For years, insulin resistance has been thought of as a consequence of chronically elevated blood sugar, where high glucose levels force the pancreas to overproduce insulin until the system breaks down. But this study challenges that perspective. It suggests that elevated insulin itself might be a primary driver of insulin resistance, flipping the narrative and pointing toward hyperinsulinemia as a root cause that can precede type 2 diabetes by years or even decades.

Practical Strategies to Lower Insulin Levels

The implications are profound. If too much insulin is indeed a key cause of insulin resistance, then strategies aimed at lowering insulin—not just blood sugar—could be more effective in preventing and managing metabolic diseases. This brings us to actionable steps. Dietary approaches like intermittent fasting or low-carbohydrate diets are known to reduce insulin levels and improve insulin sensitivity. Reducing meal frequency and avoiding refined carbohydrates and sugars are simple yet powerful ways to prevent chronic hyperinsulinemia.

Insulin Resistance Can Be Reversed

Another key takeaway is that insulin resistance is reversible. The same study showed that treating insulin-resistant cells with epigenetic modifiers restored their sensitivity to insulin. This highlights the body’s incredible capacity to heal when given the right conditions.

In summary, insulin is an essential hormone, but as with anything, balance is crucial. Chronic hyperinsulinemia, fueled by modern eating habits, can lead to significant metabolic issues. By understanding how choices impact insulin levels, individuals can take meaningful steps toward better health.

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