Summary: Insulin resistance is the primary cause of type 2 diabetes, but how it works is still poorly understood. Now a new study suggests that insulin breaking down too fast in body tissues might play a significant role in type 2 diabetes.
Insulin resistance is known to be a primary cause of type 2 diabetes (T2D). But how insulin resistance works is still poorly understood. Science holds that it mainly happens when cell receptors stop responding to insulin. Now a new study suggests a brand-new mechanism: insulin may break down faster on its way. So less of it might reach the cells where it does its work.
To follow what researchers are saying, you need to know a little about T2D. This kind of diabetes affects 90% of those living with diabetes.
We know T2D does not begin with too little insulin. It begins with insulin that does not work. Body cells slowly stop responding to it. Until now, researchers believed this insulin resistance comes mainly from changes in cell receptors. Those include receptors in liver cells, skeletal muscle, and other tissues.
But those are only theories, because the exact cause of insulin resistance is mostly unknown. What we do know is that in T2D, cells just stop responding to insulin.
For example, in early T2D, the insulin level in the body is normal or even too high. When the body stops responding to insulin, it makes even more insulin to make up for it. In the end, this wears out the beta cells in the pancreas. Then the body runs short of insulin.
But now this new study challenges the long-held view of what drives insulin resistance. It suggests the problem is not changed or deaf cell receptors. Instead, it suggests insulin breaks down faster, which leaves less insulin to act.
This is not the first study to suggest this. But until now, researchers assumed this mechanism played almost no role in T2D. This latest study suggests that is not the case. This mechanism may be the main cause of insulin resistance.
The study found that when the pancreas releases insulin, a significant part of it breaks down fast in people with diabetes. Insulin breaks down in healthy people too. But in people with T2D, it happens much faster. So insulin never gets enough time to act on the target tissues.
The good news is that researchers also found what drives this fast breakdown. The GSH/GSSG (redox) couple played a significant role. This happens because the body’s redox potential (its chemical balance between oxidation and reduction) is lower.
Of course, these results are still from early experimental studies. Still, they move our understanding of T2D one step forward. More studies are needed to learn the role of insulin breakdown in the disease. It is quite possible that this is one of the most significant drivers of insulin resistance, or just one of several.
Future studies now need to dig deeper. They need to learn how to boost redox processes in the body and counter this insulin breakdown, to better manage diabetes.
Frequently asked questions
What is insulin resistance?
Insulin resistance means the body’s cells slowly stop responding to insulin. Type 2 diabetes begins this way. It does not start from a lack of insulin, but from insulin that no longer works. In early type 2 diabetes, insulin levels are normal or even too high. That is because the body makes extra insulin to push past the resistance.
What causes insulin resistance?
The long-held view is that changes in cell receptors, such as those in the liver and skeletal muscle, stop cells from responding. This study points to a different mechanism. In people with type 2 diabetes, insulin from the pancreas breaks down much faster than normal. So less of it reaches the cells. The faster breakdown was tied to the GSH/GSSG redox couple and a reduced redox potential.
How does insulin resistance turn into type 2 diabetes?
When cells stop responding to insulin, the pancreas makes even more of it to keep up. Over time, that extra work wears out the beta cells in the pancreas. The body then goes from too much insulin to too little. Insulin resistance is the primary cause of type 2 diabetes, the form that affects 90% of people living with diabetes.
Does insulin break down faster in type 2 diabetes?
According to this study, yes. Insulin breaks down in healthy people too. But in people with type 2 diabetes, a significant part of it breaks down soon after release. So it never gets enough time to act on the target tissues. These are early experimental results. Future work aims to boost the body’s redox processes to counter that breakdown.
Source:
Cramer, C. N., Hubálek, F., Brand, C. L., Helleberg, H., Kurtzhals, P., & Sturis, J. (2024). Chain splitting of insulin: An underlying mechanism of insulin resistance? Npj Metabolic Health and Disease, 2(1), 1–6. https://doi.org/10.1038/s44324-024-00042-1
Dr. Gurpreet Singh Padda, MD, MBA, MHP
