Key points:
- Researchers used genetic data to identify 10 new loci associated with insulin resistance.
- One of the loci was located within the gene that codes for GLUT4, the protein responsible for taking up glucose from the blood into cells after eating.
- The team hopes their findings can help inform future treatments of type 2 diabetes.
A study of the DNA of more than 55,000 people worldwide has shed light on how humans maintain healthy blood sugar levels after we eat. The findings could help inform future treatments of type 2 diabetes, which affects over 460 million people worldwide.
In the study, published in Nature Genetics, researchers from the University of Cambridge used genetic data from 28 studies, encompassing more than 55,000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels two hours after ingesting a sugary drink.
The team identified new 10 loci associated with insulin resistance after the sugary drink. One of the loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. The loci were associated with a reduced amount of GLUT4 in muscle tissue.
The researchers then looked for additional genes that may play a role in glucose regulation in mouse models. This led to the discovery of 14 genes that play a significant role in GLUT 4 trafficking and glucose uptake—with nine of them never previously linked to insulin regulation.
Further experiments showed that the genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. The less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood, according to the findings.
Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.
“Our findings open up a potential new avenue for the development of treatments to stop the development of type 2 diabetes. It also shows how genetic studies of dynamic challenge tests can provide important insights that would otherwise remain hidden,” said study author Claudia Langenberg, Director of the Precision Healthcare University Research Institute at Queen Mary University of London.