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The gold of the diabetes researchers

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The cells that produce insulin and glucagon are difficult to access, as they are located inside the fragile pancreas. Researchers looking to understand how they function and what underpins the development of diabetes are therefore often advised to conduct their experiments on animals. The Human Tissue Lab, on the other hand, provides researchers with access to cells from deceased human donors; this has led to Lund University’s Diabetes Centre, LUDC, currently being ranked as one of the most outstanding within diabetes research.

Charlotte Ling is studying the influence of lifestyle on our genes in a field known as epigenetics and has benefitted greatly from the Human Tissue Lab. Among the findings from her research is evidence that age and exercise make an impression on our genes in the form of chemical changes, known as DNA methylations, and that these changes affect the ability of the beta cells to secrete insulin. She has also led a major mapping process showing how DNA methylations vary between healthy individuals and people with type 2 diabetes.

Animal experiments still needed

Within the framework of a major EU-funded research project, she is now in the process of studying the interplay between specific genes and epigenetic changes to find out how they affect genetic expression and insulin secretion.


“If we can understand how our lifestyle affects the epigenetic changes in humans, we can develop new drugs to prevent or cure type 2 diabetes”, says Charlotte Ling.


Despite the opportunities offered to the researchers thanks to the Human Tissue Lab, animal experiments are still important for studying genes, their effects and their underlying mechanisms.


“We will never be able to study everything that happens in the pancreatic islets in living people or conduct intervention studies showing exactly how the cells are affected by exercise, for example. But you cannot escape the fact that when it comes to preventing or curing diabetes in patients, human pancreatic islets are what you need to look at”, says Charlotte Ling.

The Human Tissue Lab leads to new findings

The pancreatic islets are a group of cells consisting mainly of beta cells that produce insulin and alpha cells that produce glucagon. These two hormones regulate the body’s blood sugar and metabolism. Because of their location, the pancreatic islets are difficult to study in living humans. Similarly to other organs, they are donated to research when a person dies, if not used for transplantation.


Due to the limited access to human pancreatic islets, most of our current knowledge about diabetes comes from experiments on rats and mice. We even know several ways of curing diabetes in these animals. Unfortunately, this knowledge has not always been transferable to human conditions.


“The possibility to do research on human cells has forced us to revaluate a lot of our earlier findings”, says professor Charlotte Ling at Lund University Diabetes Centre.


The Human Tissue Lab is a resource that studies and analyses the pancreatic islets on the basis of genetic variations and their ability to secrete insulin and glucagon, among other things. It can be compared to a bank in which the researchers enter and retrieve data. Since 2007, researchers have built up a completely unique knowledge bank with information on how the islets function and how they differ from healthy individuals to people with type 2 diabetes. To avoid several researchers doing the same thing, access to the material is managed through applications.


“Once you have published your results, you make the new information accessible to all those within EXODIAB”, says Professor Charlotte Ling, who is also the convener of the steering group for the Human Tissue Lab.


EXODIAB is one of the Swedish government´s strategic research area within diabetes that includes Lund University and Uppsala University.
Thanks to the Human Tissue Lab, researchers have contributed to extensive new knowledge in the field of diabetes which has resonated in the research community worldwide. Researchers at LUDC were the first to map the function of several genes in islets from humans and have identified the function of a number of previously unknown but important genes that play a major role in the development of type 2 diabetes including TCFL7, which is the single strongest risk gene for type 2 diabetes. They have also studied individual genes down to their smallest component parts and found out how different variations within them affect the risk for the disease.

 

Diabetes

Diabetes is one of the most common diseases and its incidence is increasing exponentially worldwide. Over 400 million people in the world have diabetes, and their number is expected to exceed 640 million by 2040.
Diabetes is characterised by excessively high blood sugar which, if left untreated for a long time, can lead to serious complications such as eye damage, amputations, kidney and nerve damage as well as cardiovascular disease including heart attacks and stroke.
Between 80 and 90 per cent of patients have type 2 diabetes which is caused by a combination of genetic and lifestyle factors, with too much food and too little exercise.
Type 1 diabetes is an autoimmune disease caused by the immune system destroying its own beta cells. Other forms of diabetes include LADA, MODY and gestational diabetes, as well as other more rare variants of the disease.