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Sinking ‘SHIP2’ to reduce insulin resistance

Project summary

Does Chronic Insulin Sensitisation in vivo Promote Macrophage Insulin Resistance?

Dr Matthew Gage will explore the long-term effects of reducing the activity of SHIP2 (a molecule that prevents cells from responding to insulin) in a particular immune cell. This will help them to investigate the value of SHIP2 as a target for new Type 2 diabetes therapies.

Background to research

Type 2 diabetes is a complex condition that involves many different cell types. Macrophages, a type of immune cell, have been show to play an important role in diabetes and diabetes-related cardiovascular disease. We know that macrophages in people with Type 2 diabetes are different to those in people without the condition. This results in more inflammation in tissues that are important for glucose control, which means that they respond poorly to insulin.In people with Type 2, macrophages themselves also respond poorly to insulin, with harmful consequences. The exact role of macrophages in Type 2 diabetes and how they might be targeted with new therapies is not yet clear.  SHIP2 is a molecule that prevents cells from responding to insulin. It's thought that reducing the activity of SHIP2 will restore the ability of cells to respond to insulin. This has made SHIP2 an important target for the development of new drugs, but the long-term effects of targeting SHIP2 need to be investigated. 

Research aims

Dr Gage and his team will explore the long-term effects of reducing SHIP2 activity in macrophages, to investigate its value as a target for new Type 2 diabetes therapies. This will involve studying mice that have reduced activity of SHIP2. They will compare the levels of certain genes found in these mice, to the levels in mice with normal SHIP2 activity.  The team will look at the impact of reduced SHIP2 activity on chemical pathways that affect insulin signalling. They will use cells from older mice that have had SHIP2 activity reduced for their whole lives, since this will enable them to find out if modifying SHIP2 is effective in the long term. 

Potential benefit to people with diabetes

People with Type 2 diabetes need effective treatments to manage their condition. This research aims to find out if SHIP2 has a positive impact on insulin signaling, which will inform the development of future therapies for Type 2 diabetes. 

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