An exciting study conducted at the University of Gothenburg and the Lund University Diabetes Centre presents a new mechanism for reduced insulin production in type 2 diabetes (T2D). Current theories attribute the lowered insulin levels to either a reduction in Beta-cell numbers, the insulin-producing cells of the pancreas or defects in their function. Thanks to the collaborative efforts of researchers at Gothenburg and Lund Universities, this debate has finally reached a resolution. In their study, the authors experimentally demonstrate that a reduction in the levels of insulin occurs due to both, a reduction in a number of beta cells as well as defects in their function.
A new T2D regulator: SOX5
With the gene expression data of samples from T2D individuals and non-diabetics, the team analyzed the most impactful genetic changes that affected the course of the disease. Human T2D develops through a vicious cycle, characterized by progressive changes in a range of genes leading to β-cell dysfunction.
“All airports are connected in a large network, but a disruption at a hub like Frankfurt Airport is much more serious than a disruption in Gothenburg. We searched out the hubs, i.e. the key genes, and the major links. Of almost 3,000 genes that were changed in diabetes, 168 could be described as Frankfurt genes. It was these we focused on,” said Anders Rosengren, associate professor at the Department of Neuroscience and Physiology at the University of Gothenburg.
The analysis suggested that SOX5, a gene which has not been known in the diabetes context, has a great impact in bolstering the function of the inulin producing cells and playing an important role in the maintenance of cellular identity. SOX5 suppression led to decreased levels of about 168 genes in T2D-associated pathways thereby resulting in deterioration of Beta-cell function and impaired insulin secretion. Conversely, an overexpression of SOX5 restored insulin secretion partially.
“It’s very exciting to see. It was almost like a volume control, where you could increase or decrease the maturity level of the insulin-producing cells.” Rosengren added.
The take-home message: “Prevention is better than cure”
The findings from this study also highlight the effect of lifestyle on this T2D mechanism.
According to Anders Rosengren, it will not be long before we see drugs that restore the maturity of insulin-producing cells. They may already exist as medicines used to treat other diseases.
However, the partial restoration of insulin secretion upon SOX5 overexpression after its suppression is a clear indication that Beta-cell dysfunction is not completely reversible once a plethora of related genes are perturbed in the T2D gene network. This is comparable to a case of long-standing disease in which the Beta cells have lost their identity and glucose sensitivity to secrete insulin.
Further, SOX5 reduces if you have unhealthy food and lifestyle habits (BMI > 27) and more so when you age. Therefore, Rosengren underlines that healthy lifestyle habits do play a crucial role in type 2 diabetes.
“Some manage a long time despite unhealthy lifestyle habits. For others, the tipping point is much earlier. But, regardless of genetic conditions, you can do something about your disease,” he emphasizes as a take-home message.
The original report can be found here.
Source: Sahlgrenska Academy News