What if someone said that you — someone with type 1 diabetes — could take a pill and your insulin requirements would not only drop, but they might be eliminated completely? Would you think they were crazy, or maybe confusing you with a type 2?
Well, it may not be a matter of sanity or misunderstanding. We might not be talking about a “magic pill” to make your diabetes disappear, but the early stages of research by a North Carolina man show promise for a pill-treatment down the road.
With a little work, research scientist Terry Combs thinks the pill could become a reality. In the research field for a quarter century, Terry got tired of going through the motions of doing science on animals and wanted to find a way to turn lab experiments into products that could benefit real people, not just mice. Inspired by the discovery insulin nine decades ago and his family’s history of diabetes, he decided to pursue diabetes research. He co-founded Combs Lab in North Carolina, where he serves as chief executive officer.
It was during his new venture in diabetes research that he learned about SOGA, a protein found in the liver. Like insulin, SOGA is a protein that lowers blood sugar but is missing in our systems as type 1 PWDs.
This protein is released at the same time as insulin, and it blocks the production of glucose from your liver when you’re eating. When you’re not eating, your liver continually pumps out small amounts of sugar to keep your glucose levels stable (read: the reason we need basal insulin). But when you’re eating, there’s no need for extra glucose, so the SOGA usually kicks in. Not for us PWDs, though.
“The body is really overproducing the amount of glucose it needs,” Terry explains. “The body of a type 1 or type 2 PWD overproduces glucose to different degrees. So the reason blood sugar goes so high after a meal is that you’re getting a double infusion of blood sugar, one from your own body’s production and one coming from the food in your GI track.”
Now, focusing on SOGA, Terry and his team are working on a drug that would stop the production of the body’s own glucose, akin to how a statin works to lower the body’s own production of cholesterol. Just like insulin, you can’t ingest SOGA, so the drug would be a formulation designed to stimulate the body’s own SOGA production.
Actually, researchers stumbled across this whole SOGA issue by accident…
They were exploring another hormone called adiponectin, which is interestingly higher in type 1 PWDs even though its function is normally to lower glucose. Confused, researchers theorized that there must be something broken.
A decade later, they discovered that adiponectin actually “turns on” the other protein SOGA in non-PWDs, but for some strange reason, those higher levels still don’t trigger the SOGA in type 1 PWDs. A paradox, as Terry describes it — so it follows that triggering SOGA in type 1 PWDs should help lower their glucose levels.
As you might guess, much of this work is still theory. And how do you test theories in diabetes research settings?
In MICE, of course!
In early studies, SOGA was raised in mice with blood sugar values of 400 mg/dL, and their blood sugar levels were brought down to normal levels within 4 days. When a pill that increased SOGA was given to mice with diabetes, nothing happened, leading Terry and his team to believe that SOGA could effectively lower blood sugar without causing hypoglycemia and that might eliminate the need for insulin entirely (!), at least in some people.
Wait – don’t we need insulin to get glucose into the cells? The primary method of getting glucose into cells is using a glucose transporter called Glut-4, which uses the “insulin key” to get the glucose from outside the cell. But Terry says that’s not the only way.
“There are glucose transporters in our cells that don’t require insulin to bring glucose inside,” he says. “In the lab, we have a diabetic mouse who has no Glut-4 and no effective insulin in lowering blood glucose, but you don’t see hyperglycemia and you don’t have a diabetic animal. The glucose still gets into cells and there are normal blood levels of glucose. So there are indications that it happens. We think the way that it works in a mouse is very similar to how it works in humans.”
Well, of course it works in mice… wasn’t Terry himself tired of seeing mice cured of diabetes?!
Yes, but pragmatically, you have to start somewhere safe and approved for studies, Terry points out. And the truth is that even if this did translate to humans and work out, it’s not perfect. It’s likely most PWDs would still have to take some amount of insulin at meal-times. A low-carb PWD might be able to get away with it, but most of us will probably need the assistance of insulin to keep blood sugar levels from spiking dangerous. Terry also theorizes that any residual beta cell function could potentially make up some of the difference as well, since it is believed that beta cells continue working a bit in some people for many years after diagnosis.
The research is still in its beginning stages, with Terry and his team working in the laboratory with cells in petri dishes and in animal models. But Terry envisions an oral pill that patients will take twice a day, similar to other type 2 drugs. They’re also studying how those other drugs, like metformin and TZDs, might work in combination with this future pill.
“We will figure it out as we go along,” he explains. “You could take it without measuring your blood sugar because it wouldn’t cause low blood sugar. There might end up being a fast-acting version and a slow-acting one.”
So, we’re not talking any magic bullet that’s being referred to as any kind of “cure.” But this does appear to be a new and potentially amazing possibility for people with type 1 diabetes — since our med options are very limited to date. Research continues to show that insulin is not the only hormone that our bodies are missing and need to function properly. Replacing the effect of these hormones, as is the case with Symlin, has shown to have some positive effects.
“We are stretching our imagination for the best-case scenario,” Terry says. “It’s conceivable that this pill will make a big impact on type 1 diabetes treatment. There are scientific arguments to that end and they follow reason and logic.”
Like many researchers, Terry and his team are in need of funds to further their work. In the coming weeks, they plan to launch a fundraising page on their website where people can contribute. Hopefully, they’ll be able to raise enough for research to progress, and their experimental pill proves to work beyond the lab mice…
Story of our D-Lives, right?
But we love it that people like Terry are aggressively beating new paths to ever-better treatments.