MicroRNAs - small very short sequences of RNA - were one of the subjects studied by the recipients of the 2006 Nobel prize in Physiology or Medicine as part of their work on RNA interference (RNAi). Since then microRNAs have become a very hot topic in biological research, thanks to their role in regulating gene expression, their potential for silencing genes and their effect on the immune response. A new paper to be published in the journal Diabetologia, shows that the expression of microRNAs plays a significant role in type 2 diabetes. "Everything we know about microRNAs has been from research into cancer, but microRNAs are so important for all biological processes because of the effect they have in controlling the expression of other genes," says lead author Blanca Herrera, a post doctoral researcher in the Lindgren group at the Wellcome Trust Centre for Human Genetics.
Type 2 diabetes, a form of diabetes that typically develops later in life and which has been linked with obesity, is the commonest form of diabetes. Statistics compiled by the charity, Diabetes UK, suggest that of the 2.5 million diabetes sufferers in the UK, 90% have type 2 diabetes. The disease is characterised by high levels of blood sugar (hyperglycaemia). This results when the body either does not produce enough insulin, or because cells stop responding properly to the insulin that is produced.
Previous research showing that the expression of microRNAs can affect insulin secretion prompted Dr Herrera, working with Cecilia Lindgren, University Research Lecturer at the Wellcome Trust Centre for Human Genetics, and their colleagues to consider what role microRNAs might play in the development of the type 2 diabetes. "Essentially," says Dr Lindgren, "we were faced with a chicken and egg dilemma. Are microRNAs altered because of hyperglycaemia? Or does hyperglycaemia result because of microRNA alteration?"
To explore these questions the group studied the effect of different glucose levels on micro-RNA expression in liver, muscle and adipose (fat) tissue from three inbred rat strains that differ in diabetes susceptibility. They then went on to carry out further work in order to determine the effect of changing glucose levels in microRNAs in adipose tissue.
The results of their research reveal that just 5 out of the hundreds of microRNAs present in the cells are significantly connected to glucose levels in diabetes. It also confirms that increased glucose levels do play a role in regulating microRNAs.
These results - combined with their continuing work in this area, including information from studies of microRNA in humans - will provide additional clues about the role of microRNAs and the mechanisms involved in type 2 diabetes and hyperglycaemia. This, in turn, could lead to better treatments. "It is only by fully understanding diabetes that can we hope to mitigate it." says Dr Herrera. "Because MicroRNAs can regulate many other genes, they are very attractive drug targets. Given the obvious therapeutic possibilities, we hope our findings about the role of microRNA in glucose regulation will contribute to progress towards the development of therapies."
Figure: The global expression of microRNAs in liver, fat and muscle tissue determined using microarrays. Each row represents a microRNA and each column a tissue sample.
For more information on Dr Lindgren's research, click here.