Light-activated drug could reduce side effects of diabetes medication

Scientists have created a drug for type 2 diabetes that is switched on by blue light, which they hope will improve treatment of the disease.

Diabetes drugs that promote the release of insulin from the pancreas can in some cases cause side effects due to their actions on other organs such as the brain and heart. Some can also stimulate too much insulin release, causing blood sugar levels to drop too low.

To help create better drugs, researchers at Imperial College London and LMU Munich adapted an existing type of drug called a sulfonylurea so that it changes shape when exposed to blue light.

The drug would be inactive under normal conditions, but a patient could in theory switch it on using blue LEDs stuck to the skin. Only a small amount of light would need to penetrate the skin to change the drug’s shape and turn it on. This change is reversible, so the drug switches off again when the light goes off.

In a study published today in Nature Communications, the researchers demonstrated that the prototype drug, known as JB253, stimulates insulin release from pancreatic cells in the lab when exposed to blue light.

The study was led by Dr David Hodson and Professor Guy Rutter from the Department of Medicine at Imperial College London, and Professor Dirk Trauner and Dr Johannes Broichhagen at LMU Munich.

Dr Hodson said: “In principle, this type of therapy may allow better control over blood sugar levels because it can be switched on for a short time when required after a meal. It should also reduce complications by targeting drug activity to where it’s needed in the pancreas”.

Light-activated drug could reduce side effects of diabetes medication “So far, we’ve created a molecule that has the desired effect on human pancreatic cells in the lab. There’s a long way to go before a therapy is available to patients, but this remains our ultimate goal.”

Type 2 diabetes affects around 350 million people worldwide. It impairs people’s control over their blood sugar levels, leading to higher risk of heart disease and stroke and potentially causing damage to the kidneys, nerves and retinas.

Although molecules that react to light have been known about since the 19th century, only in the last few years have scientists exploited their properties to make light-sensitive molecules with drug effects.

“Photoswitchable drugs and photopharmacology could be enormously useful for all sorts of diseases, by allowing remote control over specific body processes with light,” said Professor Trauner.

The research was funded by Diabetes UK, the European Foundation for the Study of Diabetes, the European Research Council, the Wellcome Trust and the Medical Research Council.

Dr Richard Elliott, from Diabetes UK, said: “Sulfonylureas help many people to manage type 2 diabetes even though, like other medications, they can have side effects. Work on light-activated medications is still at a relatively early stage, but this is nevertheless a fascinating area of study that, with further research, could help to produce a safer, more tightly-controllable version of this important therapy.”

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Reference: Johannes Broichhagen et al. ‘Optical control of insulin release using a photoswitchable sulfonylurea.’ Nature Communications, 14 October 2014. DOI: 10.1038/ncomms6116

About diabetes

1. In the UK, there are around 3.8 million people who have diabetes. There are 3.2 million people living with Type 1 and Type 2 diabetes, and around 630,000 more who have Type 2 diabetes but don’t know they have it because they haven’t been diagnosed. As many as 7 million people are at high risk of developing Type 2 diabetes and if current trends continue, an estimated 5 million people will have diabetes by 2025.

2. Diabetes is a condition where there is too much glucose in the blood because the body cannot use it properly. If not managed well, both Type 1 and Type 2 diabetes can lead to devastating complications. Diabetes is the leading cause of blindness in people of working age in the UK and is a major cause of lower limb amputation, kidney failure and stroke.

3. People with Type 2 diabetes don’t produce enough insulin or the insulin they produce doesn’t work properly (known as insulin resistance). 85 to 90 per cent of people with diabetes have Type 2. They might get Type 2 diabetes because of their family history, age and ethnic background puts them at increased risk. They are also more likely to get Type 2 diabetes if they are overweight. It starts gradually, usually later in life, and it can be years before they realise they have it. Type 2 diabetes is treated with a healthy diet and increased physical activity. In addition, tablets and/or insulin can be required.

4. For more information on reporting on diabetes, download Diabetes UK’s guide for journalists: http://www.diabetes.org.uk/journalists-guide

About Imperial College London

Consistently rated amongst the world’s best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial’s contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK’s first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

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Sam Wong

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Imperial College London

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