ER stress induced microRNAs in insulin resistance

The obesity epidemic has caused in a substantial increase in the incidence of type two diabetes mellitus (T2DM). Approximately 2.4 million people in Ireland are overweight/obese. Diabetes and its complications take a significant portion of the healthcare budget annually. T2DM results from the inability of the beta-cells of the pancreas to produce sufficent insulin.Ultimately, the effect of high glucose levels and insulin resistance on the beta-cells leads to their dysfunction and eventual death. Insulin resistance is defined as a condition whereby insulin is less effective at lowering the blood glucose levels. The most common cause of insulin resistance is obesity. Our research group has a keen interest in studying the role of the endoplasmic reticulum (ER) in insulin resistance and beta-cell dysfunction. The ER is a membrane network within cells involved in the synthesis, modification, and transport of materials. When the ER is exposed to 'stressors' such as the high glucose levels it begins to malfunction. Newer drugs are now available which propose to prevent ER stress and beta-cell dysfunction. It is difficult, however, to assess if this is the case as imaging the beta-cells is not a realistic possibility. We intend looking at particles called microRNAs that are secreted from cells in response to ER stress. MicroRNAs are found in the bloodstream. Our research group has discovered particular miRNAs that are secreted when there is ER stress. I will analyze the microRNA profiles in the blood of people who are obese and patients with T2DM. I will look at the effect of medication on the microRNA profiles in animal and human models. The development of agents that prevent beta-cell death resulting in T2DM is crucial.The proposed research offers the exciting possibility of discovering new markers of beta-cell dysfunction and insulin resistance and may deliver potential targets on which new and existing drugs can be developed for the treatment and perhaps the prevention of T2DM.

Award Date
26 April 2013
Award Value
€178,074
Principal Investigator
Dr Siobhan Bacon
Host Institution
University College Dublin
Scheme
Research Training Fellowships for Health Professionals