Happy Saturday! Welcome to Ask D'Mine, our weekly advice column hosted by veteran type 1 and diabetes author Wil Dubois in New Mexico, who happens to have experience as a clinical diabetes specialist. This week, Wil looks at diabetes research and those lil' lab mice that are ever so curable, yet haven't led to a human cure to date.

{Got your own questions? Email us at AskDMine@diabetesmine.com}

 

Lisa, type 1 from New Mexico, writes: I wanted your thoughts on a recently published study in the journal “Cell Stem Cell” where scientists reprogrammed Alpha cells in the pancreases of mice to produce insulin.

Wil@Ask D’Mine answers: I read the article. And the more I read, the more excited I got. This is some really, really, really good research. It was well done, and opens up some exciting new possibilities. The basic idea here was to take some other cell in the body -- one that doesn’t appear to be affected by our haywired immune system -- and teach it to make insulin. And, as you noted, the Pittsburgh-based team of scientists did more than just find any old cell in the body, they went after the Alpha cells, which are already in the pancreas. 

OK, so I guess that the idea of finding a replacement cell for the killed-off beta cells isn’t totally new, and it doesn’t solve the underlying dysfunction in the immune system. In fact, this particular approach seemed so unlikely to succeed that the investigators are actually quoted as saying they fully expected it to fail. But something wonderful and unexpected happened. But I’m getting ahead of myself. 

Here’s the deal: The investigators took some type 1 diabetic mice and successfully “reprogrammed” their Alpha cells to make insulin. So far so good. Of course, they then expected that these newly re-christened beta cells would be wiped out right away by the immune system. And they were correct. The new cells were wiped out.

But not right away.

In fact, it took four full months. That might not sound like a lot to you, but a mouse has a life span of only two years, so four mouse months could translate into decades for human beings if the process worked on us.

Excited yet?

I was. I still am. So how did they reprogram the Alpha cells?  Well, I don’t have a degree in gene therapy, so I don’t even pretend to understand what I’m about to tell you, but here goes: The scientists delivered a pair of proteins called Pdx1 and MafA into Alpha cells in the pancreases of experimental mice. More on those mice in a minute. The proteins were delivered using the gene therapy version of a FedEx truck: A virus. Once delivered, the Alpha cells quit their day jobs and started making insulin instead and the blood sugar of the mice normalized! For four months.

Uhhh… wait a minute. Just what where the Alpha cells doing before they were re-programmed? What was their original job? 

Ironically, they make glucagon, the peptide hormone that raises blood sugar. But don’t you need them? Maybe not. Apparently, the Alpha cells make only 20% of your glucagon, so reprogramming them to substitute for the dead Beta cells doesn’t completely wipe out your ability to make glucagon, which you need for glucose homeostasis (normal levels).

The idea is very appealing to me, as it would use something already in place in our bodies, so there are no rejection issues like you get when transplanting something that belongs to someone else into your body. And if a cell can be reprogrammed to create insulin, then that means you wouldn’t need to inject artificial insulin. And the Alpha cell is in the right place to start with -- in the pancreases, even in the islets. You don’t have to move it from somewhere else.

Could it be that the “cure” has been waiting inside our own bodies all of this time?

This is definitely research we should watch! But don’t get too excited yet. This study is nothing but a first step of a very long journey.

Now, as promised, more about those lab mice…

I've written about mouse research before in a 2017 column. For this study, the researchers used two types of diabetic mice. The first kind are garden-variety mice who have essentially been poisoned to kill off their Beta cells. This is probably the most common type of study mouse in diabetes. I have a several problems with using them, one of them being that it seems like a mean thing to do to the poor mice, but more importantly, I’m not sure it’s a good model. I find poisoned mice to be better proxies for poisoned people (diabetes caused by poison is rare, but not unheard of) than for “natural” diabetes. In other words, I’m not sure a therapy that reversed diabetes in a poisoned mouse would work in the more complex real-world diabetes we deal with every day.

This is why I’m uneasily grateful that science has delivered to us with honest-to-God (or honest to something) mice with type 1 diabetes. Or something very close to it. The official name for such creatures is autoimmune non-obese mice, more commonly known as NOD mice, and known in some circles as NSG™ mice after their common brand name.

Brand name?

Yes. Diabetic mice are… uh… well, they are “manufactured” and sold via mail order to researchers by a number of companies, which, while I accept the necessity of it, still makes me slightly queasy for some reason. Apparently, you can order them in any “quantity needed” here. I tired to fill out the order form for a single mouse, just to see what it would cost, but they wanted to know what university I was with before they gave me a price. I stopped there because I didn’t think my status as a part-time English instructor at a community college adult education program was going to be the proper credential needed to complete the order.

I don’t know what I was thinking, I have enough trouble with my own diabetes, why would I want a pet diabetic mouse? I guess I just had a momentary impulse to save just one mouse, although in reality, the Pittsburg mice probably lived better lives, including a long (mouse long) run free from diabetes; whereas a pet diabetic mouse would have to endure multiple insulin shots and where on earth would you prick the poor thing to check its blood sugar six times a day? CGM sensors are waaaay to big for mice. And too expensive.

Although it was unclear if they would sell any quantity needed, like a single one, I did eventually find another Mice-R-Us outfit offering a retail price of $52.90 for each male diabetic mouse and $61.80 for each a female diabetic mouse. That’s the rate for 3-week-old mice. The prices go up as the mice get older, I have no idea why, but as they have diabetes, I can only guess that, like us, they are expensive to keep alive.

But back on topic to wrap up: The Philadelphia team used both kinds of mice, the poisoned variety and the mail order type 1 variety, and the Alpha cell reprogramming worked for both of them. The abstract of the research left unclear if the Alpha cells failed in the poisoned mice after four months as well. It wouldn’t seem so, as only the immune system response in the type 1 mice is specifically mentioned.

Still, even if this couldn’t be improved upon, but could be upscaled from diabetic mice to diabetic humans, a treatment that lasted two decades?

It sure beats the hell out of six shots a day. Dare I say, “Thank God for mass-produced diabetic mice?"

But anyway, what’s next? Apparently the researchers want to see if the process works on primates. And, no, I don’t know if you can mail-order a diabetic monkey, and I’m not going to find out.

 

This is not a medical advice column. We are PWDs freely and openly sharing the wisdom of our collected experiences — our been-there-done-that knowledge from the trenches. But we are not MDs, RNs, NPs, PAs, CDEs, or partridges in pear trees. Bottom line: we are only a small part of your total prescription. You still need the professional advice, treatment, and care of a licensed medical professional.