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What role do epigenetic changes play in type 2 diabetes?

15th November 2022
graphical representation of histones

The epigenome plays a crucial role in regulating gene expression, cell differentiation and X-chromosome inactivation – and can contribute to disease when dysfunctional. In her new module for EASD e-Learning, Professor Charlotte Ling explores the ways in which epigenetic modifications contribute to type 2 diabetes.

As a principal investigator in the Epigenetics and Diabetes Unit at Lund University Diabetes Centre, Sweden, Professor Charlotte Ling is more than amply qualified as a guide to the epigenetic mechanisms implicated in type 2 diabetes. Over the last decade or so, her research group has pioneered this field of investigation, making several ground-breaking discoveries – such as genome-wide epigenetic modifications in the pancreatic islets, skeletal muscle, adipose tissue and liver of people with type 2.

“We have identified epigenetic modifications in pancreatic islets from donors with type 2 diabetes compared with controls,” says Professor Ling. “However, the question is which is the chicken and which is the egg? Do these epigenetic modifications contribute to the development of type 2 diabetes? Or are they just a consequence of the disease?”

To investigate this question, she and her team have performed a series of experiments, testing whether exposure to high glucose and lipids had direct effects on the DNA methylation and gene expression patterns already seen in pancreatic islets from non-diabetic human donors. Much of this module details the results of those studies and a wealth of other evidence in support of epigenetics playing a causal role in the pathogenesis of type 2 diabetes.

The basic science subject matter takes the lead in this module, but always with a watchful eye on how this work might be applied to clinical care. Throughout the module, basic research is interspersed with clinical application scenarios and case studies, demonstrating its relevance to clinical practice. As Professor Ling says: “It is very important to try to use our basic research – to bring it to the clinic. That is the ultimate goal.”

In this case, Professor Ling and her team have their sights set on developing blood-based epigenetic markers and new therapies. “We have analysed DNA methylation in the blood trying to develop blood-based epigenetic markers that can predict future type 2 diabetes, future diabetic complications and response to therapy in people with type 2 diabetes. Some preliminary data look promising but future research will look into this further.”  Other work by her and her team supports the tantalising prospect that epigenetic mechanisms might also provide new therapeutic targets for type 2 diabetes.

Find out more about this fascinating topic by enrolling on Professor Ling’s module, Epigenetics and the beta cell – module 2 in the EASD e-Learning Beta cell biology course.

For more on this topic, see module 1 of the Beta cell biology course, Stimulus-secretion coupling in pancreatic cells.

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Manager, Dr Eleanor D Kennedy.