Buildup of a particular kind of fat leads to problems with heart and kidney disease in people with type 1 diabetes.
But researchers at Augusta University have found a novel compound that, in an animal model, blocks the creation of the fats in the digestive system without harming the level of growth hormone, which would be important in these diabetic patients because it is often diagnosed in children.
How the compound does this could also provide a way of looking at a new therapy, one of the co-authors said.
The study, published this month in the Proceedings of the National Academy of Sciences, looked at the receptors for the growth hormone-releasing hormone. They are normally found in the pituitary gland, but in a rat model induced to have what resembles type 1 diabetes, these receptors were also found to be very prevalent in the small intestine.
There they appear to be involved in the production of chylomicrons, milky substances that are mostly triglycerides and transport dietary fat into circulation, said Dr. Maritza Romero, a research scientist in AU’s Vascular Biology Center and the paper’s lead author.
Using a compound called MIA-602, it blocked the action of these receptors and prevented the creation of the milky particles and decreased the high fat problem that often accompanies this form of diabetes and is a risk factor for cardiovascular and kidney problems in these patients.
Interestingly, the compound also seemed to help improve the function of blood vessels and the kidneys themselves, Romero said.
“It looks like the protection (from high fat levels) also has beneficial effects on vascular and kidney function,” she said. “Those are the things that are encouraging us to go further with these studies. We think that it is very promising.”
The next step is to look at human cells and potential donated samples to see whether the same thing is true in human cells, Romero said, noting that it is “a very preliminary study. It is important to validate this for translational purposes” into potential human clinical trials.
How the compound potentially does this is also intriguing, said Dr. Rudolf Lucas, an associate professor in the Vascular Biology Center and a co-author on the study. Recent research found that in type 1 diabetes there are both high levels of glucagon, a hormone that raises blood glucose levels, and glucagon-like peptide 1, which is supposed to reduce glucagon and blood glucose levels.
That peptide, referred to as GLP-1, is known to stimulate insulin production but only when glucose levels are high in the blood, and drugs that simulate it are already used in treatment of type 2 diabetes. The novel MIA 602 compound, which blocks the effect of the growth hormone-releasing hormone, appears to make GLP-1 functional again in the type 1 diabetes model.
“Therefore this would be a novel pathway that could be addressed as a potential therapeutic target,” Lucas said.
What was their biggest concern, that the compound would drop growth hormone levels generally in the blood, turned out not to be true at this dose level, he said.
“That would be absolutely terrible in children,” Lucas said.
Though type 1 diabetes was once considered a disease in children, the majority of the estimated 3 million people in the U.S. with the condition are adults, according to the American Diabetes Association. This is because patients with type 1 diabetes are living longer and more adults are being diagnosed with it, the group said.
Finding that there was some systemic protection from the compound, at least in the rat model, “was very encouraging,” Romero said.