Key mechanism involved in type-2 diabetes identified
Washington: In a new study, researchers have discovered a key protein that regulates insulin resistance, which is the diminished ability of cells to respond to the action of insulin and which sets the stage for the development of the most common form of diabetes.
This breakthrough points to a new way to potentially treat or forestall type-2 diabetes, which is a rapidly growing global health problem.
In the study, Katerina Akassoglou and her team from Gladstone Institutes, describe an unexpected role of the p75 neurotrophin receptor in controlling how the body processes sugar. Called p75NTR, this receptor protein is usually associated with functions in neurons.
“We identified that p75NTR is a unique player in glucose metabolism,” Akassoglou said.
“Therapies targeted at p75NTR may represent a new therapeutic approach for diabetes,” she said.
The pancreas makes a hormone called insulin that processes glucose, moving it from the bloodstream into the body’s cells where it is used for energy. Insulin resistance is a key feature of Type 2 diabetes, in which glucose builds up in the bloodstream and the body’s cells are unable to function properly.
According to the Centers for Disease Control and Prevention, more than 20 million Americans have type 2 diabetes.
“Type 2 diabetes has become a very serious health problem and it is increasing at an alarming rate,” Lennart Mucke, who directs the institute in which the research was conducted, said.
“These findings provide an important new avenue for developing better therapies to combat this deadly disease—the seventh leading cause of death in the United States,” Mucke said.
Complex signalling interactions between several different types of tissue—including fat, liver, muscle and brain—regulate glucose metabolism. Because p75NTR is found in fat and muscle tissue and participates in many important functions in the cell, Gladstone scientists hypothesized that p75NTR might also help to regulate glucose metabolism.
To study this, the researchers used mice that lacked the genes for p75NTR. They compared these mice to normal mice and discovered that those lacking p75NTR were more responsive to insulin when fed a normal diet. Second, they used some molecular biology tricks to block the action of the p75NTR protein in fat cells.
This also resulted in increased glucose absorption in response to insulin. In contrast, when they caused the fat cells to make more p75NTR, glucose absorption was reduced. Additionally, the researchers found that another important regulatory molecule, Rab5, played a key role in p75NTR``s impact on metabolism.
“Importantly, regulation by p75NTR enhanced insulin’s effectiveness in normal lean mice on a normal diet,” Bernat Baeza-Raja, lead author of the study, said.
“Because these mice already process glucose efficiently, the actions of p75NTR on glucose transport indicate a direct role of this protein in the regulation of glucose metabolism,” Baeza-Raja said.
The study will be published online in the Proceedings of the National Academy of Sciences.