Health & Medicine, UK (Commonwealth Union) – A study of the DNA of over 55,000 individuals across the globe has given new insights on ways we keep healthy blood sugar levels following meals with implications for our knowledge on ways the process goes wrong for type 2 diabetes.
The latest findings, appearing recently in Nature Genetics, have the potential to contribute valuable insights for future treatments targeting type 2 diabetes. This prevalent condition affects approximately 4 million individuals in the UK and over 460 million people across the globe according to researchers.
Various factors contribute to an elevated risk of developing type 2 diabetes, including advanced age, excessive weight or obesity, physical inactivity, and genetic predisposition. If left untreated, type 2 diabetes can lead to complications such as eye and foot issues, nerve damage, and an elevated likelihood of heart attacks and strokes.
Insulin, a hormone responsible for regulating glucose (blood sugar) levels, plays a crucial role in the development of this condition. Individuals with type 2 diabetes struggle to properly regulate their glucose levels due to either inadequate insulin secretion in response to elevated glucose levels, such as after a meal, or reduced sensitivity of their cells to insulin—an occurrence known as “insulin resistance.”
Previous studies on insulin resistance primarily focused on the fasting state, which occurs several hours after a meal when insulin primarily acts on the liver. However, considering that most of our time is spent in the fed state, where insulin affects our muscle and fat tissues, it is vital to understand the molecular mechanisms underlying insulin resistance after a glucose challenge, such as consuming a sugary drink or a meal. These mechanisms play a significant role in the development of type 2 diabetes, despite their current limited understanding.
Professor Sir Stephen O’Rahilly, who is Co-Director of the Wellcome-MRC Institute of Metabolic Science from the University of Cambridge, says “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population and whether it’s relevant to the risk of getting type 2 diabetes.”
A group of global researchers conducted an investigation to explore these mechanisms by utilizing genetic data from 28 studies, which involved more than 55,000 participants who did not have type 2 diabetes. Their aim was to identify significant genetic variations that influenced insulin levels measured 2 hours after consuming a sugary drink.
Through their research, the team successfully discovered 10 new loci, which are specific regions of the genome, that were associated with insulin resistance following the consumption of a sugary drink. Notably, eight of these regions were also found to be linked to a higher risk of developing type 2 diabetes, emphasizing their relevance in the context of the disease.
Among the newly-identified loci, one was situated within the gene responsible for encoding GLUT4, a crucial protein involved in the uptake of glucose from the bloodstream into cells after meals. This particular locus was associated with a decrease in the amount of GLUT4 present in muscle tissue.
In seeking out more genes that could have a part in glucose regulation, the scientists turned to cell lines obtained from mice to asses specific genes in and around these loci. This brought about the discovery of 14 genes having a key role in GLUT 4 trafficking as well as glucose uptake, with 9 of these that had not been associated with insulin regulation.
Further research indicated that these genes played a role in how much GLUT4 was observed on the surface of the cells, likely by changing the ability of the protein to be transferred from inside the cell onto its surface.
