Summary: Insulin resistance is the primary cause of type 2 diabetes, but its underlying mechanism remains poorly understood. However, one of the new studies suggests that faster insulin degradation in various 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). However, the mechanism of insulin resistance is still poorly understood. Science believes that it mainly occurs when cell receptors stop responding to the insulin, resulting in insulin resistance. However, now, one of the new studies suggests a completely novel mechanism, suggesting that insulin may be degrading more quickly on its way. Thus, less of it might be reaching the sites of action or cells.
To understand what researchers are talking about, people need to have some understanding of T2D, a kind of diabetes that affects 90% of those living with diabetes.
It is known that T2D begins not due to insulin deficiency but rather due to its inaction, which means that body cells just increasingly stop responding to insulin. Till now, researchers have believed that this insulin resistance occurs mainly due to some changes in the cell receptors, like those found in liver cells, skeletal muscles, and other tissues.
However, those are hypotheses, as the exact mechanism of insulin resistance is largely unknown. What is known 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 excessive. When the body stops responding to insulin, the body starts producing even more insulin to compensate. However, this ultimately exhausts beta cells in the pancreas, resulting in insulin deficiency.
But now, this new study challenges the long-held view regarding the underlying mechanism of insulin resistance. It suggests that this resistance is not due to some changes or irresponsive cell receptors. This is rather due to faster insulin degradation, which leaves less insulin to act.
This is not the first study to suggest this, but till now, researchers have assumed that this mechanism hasa negligible role in the development of T2D. However, this latest study suggests that this is not the case, and this mechanism may be the prime cause of insulin resistance.
This new study found that when insulin is released from the pancreas, a significant part of it is quickly degraded in those living with diabetes. Of course, insulin undergoes degradation even in healthy people, but in those living with T2D, it happens at a much faster pace, and thus, insulin never gets enough time to act on the target tissues.
What is good about the study is that researchers have also identified the cause of this faster insulin degradation. They found that the GSH/GSSG (redox) couple played a significant role in faster insulin degradation. This happens due to the body’s reduced redox potential.
Of course, these results are still from early experimental studies. Nonetheless, it is one more step forward in enhancing our understanding of T2D. More studies are still needed to understand the role of insulin degradation in the condition. It is quite possible that this may be one of the most significant mechanisms underlying insulin resistance or just one of the mechanisms.
Future studies now need to explore this topic in more detail and understand how to boost redox processes in the body and counter this insulin degradation for better diabetes management.
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
