Shining a light on diabetes treatment

27 October 2014

Interview with

Dr David Hodson, Imperial College London

Type 2 diabetes affects around one in ten of the UK population and costs roughly £1 Diabetesmillion per hour to treat. Diabetics can't control their blood sugar levels properly because they can't make enough of the hormone insulin. One way to manage the condition is with strict control of weight and dietary intake.

Drugs that boost insulin levels can also help, although they come with side effects that can cause long-term health problems. But now a team at Imperial College have been working on a way to increase the effectiveness of a common diabetic drug called sulphonylurea, by shining light on it, as David Hodson explains to Kat Arney...

David -   We've based our drug on a sulfonylurea which has been around since the 1940s.  It was discovered just after the World War.  What this drug does is it binds to cells in the pancreas and increases their ability to release insulin.  So, what we've done is we've taken this drug and we've made it photoresponsive.  So, that means it becomes active when we illuminate it using a light.

Kat -   Can you show me then?  How does this work?  We've got some pictures here.

David -   So, this is basically the molecule here.  This is the 3 dimensional structure of the molecule but what you will see is that when we light the molecule, it changes shape.  So, when it's illuminated, the molecule becomes smaller and this increases its ability to function in the pancreas to release insulin.

Kat -   It's bent in half and that makes it more effective basically.

David -   Essentially, yeah.  The reason it does this because it contains a special chemical structure called an azobenzene.  Most people are familiar with these structures because they're used in dyes.  They're very colourful so they can be purple, they can be orange.  But the reason they're colourful is they absorb light.  So, it's this property which we've taken here and inbued upon our molecule.

Kat -   Then what happens?  You've got this molecule that bends in light.  So, how do you get it to where it's needed?

David -   At the moment, we've only really sort of looked at this in vitro sort of in test tubes and in tissue from human donors.  But what we do know is that when you apply - this is an example here.  You can see nothing happens to the cells in the pancreas.  This is a recording here.  As soon as we switch the light on, you can see the cells beginning to flash and flicker, when the cells are flickering like this, that means they're releasing insulin.  Essentially, we can turn it off.  I've just turned the light off now and these cells are doing nothing.  So, we can switch it on and off very quickly to increase how the cells activate to release insulin.  In terms of using this in humans, well we're obviously quite a long way off.  I mean, this is not sci-fi.  This functions well in the lab but we need to figure out ways in which we can non-invasively deliver light into the human body.

Kat -   Yeah, because your pancreas is quite deep inside and then how you get to blast it?

David -   I guess one of the other problems with diabetes is that it's mainly associated with obesity.  So, you've got to get this light into some fairly large abdomens as well.  But one of the beauties about this compound is it's extremely light sensitive.  So, it only needs a little bit of light to activate.  So theoretically, you should be able to get light through into your abdomen.  I mean, a good one is when you were a kid and your parents let you camp in the garden with your mate and you've got a torch.  So, you stick the torch in your mouth and you illuminate it in the dark and you see instantly - light obviously penetrates through the skin, but whether we can get this into the abdomen, we need to begin to investigate and we're currently getting those studies underway to see if this is going to be a practical possibility.

Kat -   Say that it does work, what could be the benefits of making this much more targeted?

David -   One of the benefits is that, when you think about a drug, it's like taking a sledgehammer to crack a nut.  It's going to work on its receptors in many different tissues throughout the body.  This causes side effects, undesirable side effects.  So, being able to target a drug to where it's needed is incredibly important as a refinement to treatment.  But also, it allows you to switch on and off drug activity when required.  This is particularly important here because if you think about it when you need to release insulin, it's after you just ingested food and had a meal.  So ideally, you would switch the drug on, release insulin after you've ingested food and then switch it off.  This stops you kind of overstressing the cells and releasing too much insulin.

Kat -   So, you can almost imagine sitting down and you have your meal and then quickblast of light, off you go.

David -   Exactly, yeah.  They'res some way off, but I mean, the hope would be, you would sort of have like some LEDs attached to you, something no bigger than a Nicorette patch or something like that and then you would literally just remote control it.  you would just switch it on using Bluetooth or your telephone and then this would switch the drug on and allow you to pack away the glucose.  So, it's not causing any undesirable effects.

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