Gut reaction: new ways to make insulin

08 July 2014

Interview with

Domenico Accili, Columbia University

Around 400,000 people around the UK are affected by Type 1 diabetes - a condition Insulin pumpwhere the immune system attacks their pancreas, destroying the cells that make insulin, the hormone that regulates blood sugar levels.

People with Type 1 diabetes need to monitor their blood sugar levels throughout the day and even during the night, and inject themselves with the right amount of insulin when it's needed. It's an effective treatment, but it's cumbersome.

Now Domenico Accili and his team at Columbia University in New York have made a step towards finding a solution - tricking cells in the gut into producing insulin. Kat Arney spoke to him to find out more about the idea behind the research...

Domenico -   A couple of years ago, we made a rather serendipitous observation that we could trick cells in the gastrointestinal tract, in the gut, to start doing what insulin producing cells in the pancreas normally do.  And that is to turn into an insulin factory.  It was an exciting observation, but it was made in laboratory animals.  And so, we did not know if this had any clinical application.

Kat -   So basically, you're tricking cells into turning from gut cells into pancreas cells.

Domenico -   We're really tricking an endocrine cell, the hormone-producing cell in the gut to become an insulin-producing cell.  So, the cell is already in some way primed to...

Kat -   To make stuff.

Domenico - make stuff and to secrete it.  We're simply retraining it, if you will.

Kat -   So, you've made these discoveries in animals in the lab.  How are you now trying to take this forward to humans?  What's the new discovery about?

Domenico -   The next step in this research is to make a drug that could be administered to patients and do what we've done to patient cells in the test tube and is described in the study.  It's to develop an inhibitor of the gene that we targeted as the key regulator of this process and produce it in a formulation that would be effective as a drug to be delivered to a living individual with the disease.

Kat -   So, this is kind of a molecular re-trainer, a drug that can retrain these cells.

Domenico -   That's right.  We know that if we could administer to people the same reagents that we've used in the test tube, they would probably do so.  But the one important caveat is that what we've used in the test tube is not safe for use in humans.  And so, we need to change the way in which we approach this a little bit, in response to the appropriate cues.

Kat -   So, the technique that you've used, is that the kind of thing that could work in patients?

Domenico -   Yes.  One of them would certainly be applicable to human beings.  In fact, variations of this technique have been used to cure macular degeneration in the eye or they're used to cure elevated cholesterol levels to reduce elevated cholesterol levels and prevent heart disease.  Clearly, one of the approaches would be applicable to human beings, with patients with type 1 diabetes.

Kat -   Now, there are probably many of our listeners who either know someone with type 1 diabetes or maybe have it themselves and although insulin injections are very effective, it's something that's a lifetime of medication and the health problems that go along with that.  I'm sure people are going to be wanting to know, how soon can we get this?  Where do you see this going?

Domenico -   I don't want to give any false sense of hope that we're going to come up with a treatment tomorrow.  Treating type 1 diabetes requires that whatever we propose as an alternative to insulin be as safe and as effective as insulin is, just more practical.  We can't go out on a limb with something of unproven safety or efficacy.  I know that especially the type 1 diabetes community has become understandably a little bit jaded by the constant drumbeat of new discoveries that promise to turn their lives around in a dramatic fashion.  The next step will take us probably 18 to 24 months to come up with a chemical substance, a chemical entity that could be tested at least preliminarily in humans.  And so, it's not going to be another 10 years.  It's not 6 months, but it's an ongoing effort that we're trying to press on with this rapidly and effectively as we're able.

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