DNA study reveals how we maintain healthy blood sugar levels after meals

A recent study published in Nature Genetics focused on unraveling the mechanisms behind maintaining healthy blood sugar levels after meals and how these processes can malfunction in individuals with type 2 diabetes. The research involved the analysis of genetic data from over 55,000 participants worldwide.

Type 2 diabetes is characterized by elevated blood sugar levels and is influenced by various factors such as age, obesity, physical inactivity, and genetic predisposition. If left untreated, it can lead to complications like cardiovascular issues and nerve damage.

Insulin, a hormone responsible for regulating blood sugar levels, plays a pivotal role in the development of type 2 diabetes. People with this condition either do not produce enough insulin in response to rising glucose levels after a meal or their cells become less responsive to insulin, leading to insulin resistance.

While most previous studies on insulin resistance have focused on the fasting state when insulin primarily acts on the liver, this study aimed to investigate the molecular mechanisms underlying insulin resistance after a glucose challenge, which reflects the fed state when insulin acts on muscle and fat tissues. Understanding these mechanisms is crucial since we spend a significant portion of our time in this fed state.

To shed light on these mechanisms, the researchers examined the genetic data of thousands of individuals without type 2 diabetes. Their objective was to identify specific genetic variants that influence how our bodies regulate blood sugar levels after meals, potentially leading to improved treatments for the condition.

The study involved the analysis of data from 28 studies, encompassing over 55,000 participants who did not have type 2 diabetes. By examining genetic information, the researchers aimed to pinpoint genetic variants associated with insulin levels measured two hours after consuming a sugary drink, a reflection of blood sugar regulation after a meal.

The analysis revealed 10 previously unidentified genomic regions, or loci, that correlated with insulin resistance following the sugary drink. Notably, eight of these loci were also associated with an increased risk of developing type 2 diabetes, indicating their relevance to the disease. Intriguingly, one of the newly identified loci was situated within the gene responsible for producing the GLUT4 protein, which is instrumental in transporting glucose from the blood into cells after eating. This particular locus was linked to reduced GLUT4 levels in muscle tissue.

To delve deeper into the genes involved in glucose regulation, the researchers turned to mouse cell lines. They focused on studying specific genes within and around the identified loci, leading to the discovery of 14 genes that significantly impacted GLUT4 trafficking and glucose uptake. Remarkably, nine of these genes had not been previously associated with insulin regulation.

Further experiments demonstrated that these genes influenced the presence of GLUT4 on the cell surface by potentially affecting the protein's intracellular movement. A decrease in GLUT4 reaching the cell surface compromised the cell's ability to remove glucose from the bloodstream.

Dr. Alice Williamson, who conducted this research as a Ph.D. student at the Wellcome-MRC Institute of Metabolic Science, underscored the study's significance in unraveling fundamental mechanisms of our bodily functions and understanding how dysregulation of these mechanisms contributes to type 2 diabetes.

The researchers believe that comprehending the mechanisms involved in blood glucose regulation after meals can serve as an early indicator of an increased risk of type 2 diabetes. This newfound understanding may pave the way for the development of innovative treatments in the future.

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The study was conducted with the support and help of Wellcome, the Medical Research Council, and the National Institute for Health and Care Research.