A recent Yale study discovered a new protein target for type 2 diabetes that has the potential to revolutionize type 2 diabetes treatment.
Published in Nature Communications on Aug. 31, the study found that the protein MARCH1 contributes to insulin resistance in patients with type 2 diabetes. MARCH1 damages the insulin receptors, the areas of the cell that are activated by insulin and thus allow the hormone to perform its function. Insulin plays a major role in regulating the amount of sugar in the blood and ensuring that the body has enough energy to function. Insulin resistance ultimately causes diabetes, according to the American Diabetes Association. With the knowledge that MARCH1 contributes to an individual’s proclivity to type 2 diabetes, scientists can find pathways to prohibit the functions of MARCH1 and thus hinder the development of insulin resistance, according to the study.
“Type 2 diabetes is a global epidemic, really,” study co-author Max C. Petersen MED ’18 explained. “The incidents and prevalence of type 2 diabetes continues to grow in parallel with increases in obesity, and it’s a major public health problem that will need to be addressed for our generation if our generation were to keep the population healthy.”
In the U.S. alone, 29.1 million people suffer from type 2 diabetes, according to Healthline. The disease represents the seventh most common cause of death in the United States, and the number of sufferers appears to be increasing. According to the Joslin Diabetes Center, diabetes is the most common cause of blindness in adults 15 to 64.
According to Arvindhan Nagarajan, study co-author and research scientist at the medical school, the study had three major phases. First, the scientists genetically screened the human genome for all 616 different ubiquitin ligases, proteins that regulate the turnover or termination of other proteins in the cell. They looked to find if any were related to insulin resistance.
After identifying MARCH1 as a possible factor in insulin resistance, the Yale scientists looked to see whether this relationship existed in a living-animal model. They observed the genetic makeup and DNA sequence of three different mice: a control mouse, a MARCH1 knock-out mouse, and a mouse that had the overexpression of MARCH1. In other words, they looked at a normal mouse, a mouse without MARCH1, and a mouse that had a greater-than-normal amount of MARCH1. They found that the mouse with a high amount of MARCH1 had induced insulin resistance even without the introduction of a high-fat diet.
The third stage was the process of understanding how MARCH1 functions with respect to other proteins and the cell itself on a molecular level. Ultimately, the study concluded that MARCH1 does play an important role in the level of insulin resistance in a cell.
In the early 1970s, little was known about the function of insulin and how information was transmitted from the insulin receptors to the cell.
Even after decades of research, “to some extent it remains a mystery why this phenomenon of decreased surface insulin receptors in type 2 diabetes occurs,” Petersen noted.
Recent studies have focused on other, more tertiary roles in insulin signaling and response, rather than the insulin receptors themselves. Petersen said this study looks at the most important role in insulin regulation and aims to identify a target to control the level of insulin receptors on the cell’s surface. He also noted that MARCH1’s relationship with insulin receptors is likely only one of the many important targets of the gene. While the study offers insight into the mechanisms of type 2 diabetes, more can still be learned about the gene MARCH1 and its functions.
Insulin was first introduced as a treatment for diabetes in 1922.