Anti-Inflammatory Protein from the Liver Appears to Cure Type 1 in Mice
Diabetes Health has always been ambivalent when it comes to reporting diabetes research that involves mice. For one thing, although the critters are mammals, it's a stretch to say that what happens in a mouse can be duplicated in a human.
For another, research involving animals is only the first step in a long process. The laboratory breakthroughs so breathlessly hailed today may take five or ten years to work their way to trials with humans.
But despite those misgivings on our part, there are times when news from the labs produces a genuine hope that the war on diabetes has reached a significant turning point. This is one of those times.
Two teams of researchers have found that in mice with type 1 diabetes, a protein commonly used to treat pulmonary disease-related inflammation can restore insulin-producing beta cells and normal blood glucose levels. In some cases, the disease has been entirely cured. The protein, alpha1-antitrypsin (AAT), is produced in the liver and functions as an anti-inflammatory agent.
Previous theories about type 1 diabetes have proposed that inflammation is a result of the disease, not one of its causes. But the researchers, from the University of Colorado Health Science Center in Denver and Harvard Medical School in Cambridge, Massachusetts, knew from breakthrough research published in 2007 that inflammation and insulin resistance play a significant role in the onset of type 1.
Maria Koulmanda, PhD, an associate professor of surgery at Harvard Medical School, and her colleague, Terry Strom, MD, a professor of medicine at Harvard Medical School, hypothesized that inflammation triggers insulin resistance and faulty insulin signaling and is a primary instigator of T-cell attacks on pancreatic beta cells, which eventually destroys the ability of type 1 patients to produce their own insulin.
The teams also knew that AAT has been used for years to reduce inflammation in such respiratory conditions as chronic obstructive pulmonary disease and an inherited disorder that manifests much like emphysema.
They reasoned that by using AAT to lower the levels of muscle and fat inflammation in mice, they could restore insulin responsiveness and stop T-cells from mistakenly attacking pancreatic beta cells.
Results bore out their hopes. Administering AAT to non-obese diabetic mice not only lowered inflammation levels without interfering with T-cells' normal immune system tasks, but also restored insulin sensitivity, normal insulin signaling, and normal blood glucose concentrations.
The most striking result, said Koulmanda, was that the mass of still functioning beta cells in the mice expanded-something not seen before in research into type 1.
Great Implications for Transplants
The positive results from AAT amounted to a virtual cure for type 1- in mice. However, the implications for the use of AAT in humans are profound.
Typically, about half of transplanted cells are killed by inflammation within hours after being introduced into a patient's body, and the remainder die from inflammation within five years. In contrast, although the Colorado team treated their mice with AAT for only 14 days after transplanting beta cells into them, the cells survived and functioned for 120 days.
Thus, AAT may function as a "shield," protecting transplanted beta cells from inflammation long enough to allow them to thrive and reproduce. It is also possible that in patients with recently diagnosed type 1 who retain some functioning beta cells, AAT could similarly serve as a shield to prevent further beta cell loss.
AAT's effectiveness is something that researchers will want to test with human beta cell transplant recipients. Fortunately, AAT has been used in the medical community for more than 20 years, apparently with a good safety record. Researchers say that despite its powerful anti-inflammatory capabilities, the protein does not appear to interfere with the body's normal immune responses. This means that AAT may more quickly clear the regulatory hurdles in its path to use with human patients who have diabetes.