Mapping type 2 diabetes metabolic dysregulation in different organs
Researcher from Uppsala University, led by SciLifeLab researcher Claes Wadelius, have demonstrated that patients with prediabetes or type 2 diabetes have a much more disturbed metabolism than previously believed. They also showed that the metabolism varies between different organs and disease severity. The study, which is a collaboration with Copenhagen University and AstraZeneca, among others, has been published in the journal Cell Reports Medicine.
Type 2 diabetes patients suffers from insufficient secretion of insulin from the pancreas but also reduced insulin sensitivity in several organs. To look closer at exactly what is happening in these organs, a research team from SciLifeLab and Uppsala University, started to investigate proteins, both in cells from the islets of Langerhans, as well as cells from insulin dependent systems, such as the liver, skeletal muscles, fat and blood.
When comparing samples from healthy individuals, individuals with type 2 diabetes, and prediabetes – a specific stage before fully developed type 2 diabetes – the researchers found that the disturbance in the metabolic pathways were far greater than previously believed. The alterations also became greater in every stage of the disease.
“We detected many protein levels that were either higher or lower than normal in tissues from people at different stages of disease. People with prediabetes displayed major alterations that are associated with inflammation, coagulation and the immune system in the pancreatic islets. In fully developed type 2 diabetes there were more widespread abnormalities, for example in lipid and glucose metabolism and in energy production in the liver, muscle and fat,” says last author Claes Wadelius, in a press release from Uppsala University.
All tissue samples, from healthy individuals and from different stages of disease, came from the strategic initiative EXODIAB, which is led by Professor Olle Korsgren in Uppsala. By using novel methods, the researchers were able to quantify thousands of proteins from each organ, thus enabling them to paint a detailed metabolic picture, something that has not previously been possible.
“The techniques for measuring proteins have evolved rapidly in recent years and our colleagues at Copenhagen University who participated in the study are world leaders in the field,” says Dr Klev Diamanti, who developed a new analysis strategy and performed the analyses in Uppsala together with Associate Professor Marco Cavalli and Professor Jan Eriksson.
The data from the study points to new potentially causal mechanisms of the disease, which could be further investigated in the hunt for new ways to treat or prevent type 2 diabetes.
“Our results may also support the development of simple tests that can identify people at high risk of diabetes and its complications, and also guide which type of intervention is best for the individual,” says Jan Eriksson.
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