COMMENTARY

EASD Science:  Beta Cells in the Eyes for T1D

Professor Guy Rutter

Disclosures

September 25, 2020

Professor Guy Rutter on the latest scientific advances and the honour of delivering EASD's 14th annual Albert Reynold Lecture.

This transcript has been edited for clarity.

Hi, my name is Guy Rutter, I'm a professor of cell biology and functional genomics at Imperial College in London.

What was the main theme of your lecture?

My lecture, the named lecture on behalf of Albert Reynold was around the control of insulin secretion, which is something that we all need to do in order to produce the hormone, which is the only one capable of lowering blood glucose levels. And so if we don't produce enough of that hormone, then ultimately, and as night follows day, we will develop the disease of diabetes mellitus. So my focus is around the ways we might be able to encourage the body to produce more of that hormone under conditions and in people where enough is not made.

What's the pathway from scientific theories, DNA, and animal studies to humans in clinical practice?

There are a number of pathways. Although it may seem as though we live in a sort of ivory tower, as it were, and don't really think about how this is quickly going to get to patients, in fact, we do have interactions with drug companies. I interact with one of the largest drug companies in South Asia, as it turns out, and at that point, we get very close to helping the developers there to improve existing therapies for the disease.

We actually work with synthetic chemists who improve on some of the drugs that exist. And that's very exciting because we're involved in the trials of those drugs in pre-clinical models, but also in human beings. So actually, we're closer to people in the clinic than might have been apparent in my lecture.

What are the most promising avenues you're exploring at the moment?

One is the drugs that I just referred to; these are modified versions of natural hormones that are produced from our guts, from our intestines, and they're called incretins. And we know that if we introduce these artificially, either through injection or in new formulations by mouth, that these stimulate the pancreas to make more insulin. This company with our help is developing new versions of those which last longer in the bloodstream, [so] have to be given less frequently, and have really beneficial effects: they help people to lose weight as well as to make more insulin, and so control their blood glucose better.

We think that that will improve the quality of life for patients who take them and also, you know, life expectancy and so forth. So that's quite an exciting avenue.

Is the work about managing diabetes as a disease or are we ever talking about a cure?

We are talking about cure. Some of the work that I presented was an approach called bariatric surgery, which many people will have heard of - the different ways that we can surgically intervene in the patient. And these were historically ways which have been used to treat those who are overweight, and often those who are morbidly obese. But we know that when we intervene in this way that we have really huge benefits on blood glucose and people who suffer also with diabetes.

By the way, the drugs that I talked about a second ago, what they try to do is to mimic some of the effects that the surgery causes, that's to say that the surgery enhances the production of those hormones, and we're trying to bypass that, as it were, with the drugs.

However, a lot of our work has explored and shown how that surgery actually acts, not on the gut where the actual scalpel goes in, so to speak, but in the pancreas, and to explore the signals, the messengers in the bloodstream that cause the pancreas to produce more insulin.

So our work is using some, we like to think, clever ways in which we can actually visualise the changes in the cells that make insulin, and understand what's going on to elicit this enhanced secretion. And again, this, we hope, gives us new ways, new ideas about how we can mimic that with pharmacology and avoid the surgeon's knife and provide a drug which will do the same thing.

Are there predictions you can make about what we might see in this space over the coming years?

Well, there are two things: the surgery that I just referred to, in causing people to lose weight and to change their appetite; we do know and there has been an exciting trial in the UK recently called the DIRECT trial, which has shown that people [who] simply, although it's not all that simple, severely reduced their food intake can not only have improvements in their diabetes, but in some cases, actually will recover completely.

So you asked me a moment ago, whether there is a cure. Well, it turns out that there is. It takes a lot of discipline. And I see that milder forms of that severe caloric restriction are likely to be useful, perhaps in combination with surgery in some patients; perhaps in combination with drugs, but taken together changes in lifestyle, so people lose weight, I think for type 2 diabetes holds a huge promise and huge hope. It's not just the case that only drugs are helpful, but the more we know about lifestyle changes, then the more I think we can, through behavioural and pharmacological approaches, have much better outcomes in the disease.

Type 1 diabetes is always going to be more difficult, though isn't it?

It is, but there's excitement there, in terms of producing in the test tube cells that will replace those which are destroyed by the immune system in type 1 diabetes.

There have been huge advances in the past 5 to 10 years in approaches that allow us to take cells from a patient, just skin cells for example, and in the test tube in the laboratory, convert them into cells that will make insulin, which can be then engrafted, transplanted into subjects. And we are involved in studies that tried to develop new places in the body, new sites of engraftment, which can be used.

And if you're squeamish, this may sound a bit odd. But one place we are now putting those cells is into the front of the eye. Now, of course, in subjects who are already blind, this is of course not a concern at all. But we think we can do this safely even patients who are normally sighted. The great advantage of siting those pancreatic islets there, as opposed to injecting them into the liver as has been done traditionally, is that we can monitor those cells, we can see them. If we put a microscope into the front of the patient's eye, we can see how we're doing. And therefore we can control the amount of immunosuppression that might need to be given to prevent their destruction, or we can top up those cells if they seem to be dying off or not working very well.

So yeah, there have been substantial advances in treatment of type 1 diabetes, and I think they are going to continue.

How did you feel about being asked to deliver the lecture?

Well, I wouldn't be human if I were to say anything than it is a huge honour, as I mentioned, right at the beginning of the lecture, the lecture is named for Professor Albert Reynold, who established the institute in Geneva, where I spent 2 very, very happy years 30 years ago, almost. And so it was great to be able to acknowledge that contribution to science, Europe-wide. And of course, it's a great pleasure to be able to acknowledge those people who've helped me down the past two or three decades in achieving what we've been able to achieve. So yes, it's an honour; it's a privilege. And it's a huge pleasure to do it.

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