The cycle of inflammation. B cells communicate via cytokines with other inflammatory cells, such as T cells and macrophages, to maintain and amplify the cycle of inflammation (http://www.roche.com/pages/downloads/photosel/061106/html/detail_3.html)
Diabetes is a major global health problem. In the USA alone there are some 25.8 million people living with the disease. Diabetes costs the US healthcare system more than $200 billion dollars each year. It’s a problem that is likely to further explode in the next few years. Consequently new treatments are of the upmost importance.
There are two types of diabetes: type 1 and 2. The hormone insulin is a major player in the development of the disease. Insulin has an important role in the body and works alongside glucagon to regulate blood sugar. The most common is type of diabetes is type 2 (90-95% of cases). It is caused by insulin insensitivity and eventual loss of insulin production in the pancreas.
Diabetes is highly related to stress. New research has discovered a key molecule that works to amplify this stress early on the diabetes process. This molecule is called thioredoxin-interacting protein (TXNIP). It is central to the inflammation process and leads to the death of insulin secreting B cells in the pancreas.
B cells can be thought of as the factories of the pancreas producing vast amounts of insulin every minute. Great fact:
“There are a billion or so beta cells in the average healthy pancreas. These cells will make more copies of insulin every year than there are grains of sand on every beach and in every desert in the world”
B cells and every other cell rely on an organelle called the endoplasmic reticulum (ER). This organelle works to package, tag and dispatch all the proteins, including insulin, from the cell. Diabetes comes about when the ER becomes stressed and faulty (maybe due to the need to overproduce insulin). When this occurs proteins are not packaged properly and accumulate within the B cell. The body’s response to this malfunction is drastic; it effectively destroys the cell. It does this by activating the interlukin-1 (IL-1) pathway and therefore inducing apoptosis.
This in its self is not as bad as it sounds, because our bodies have B cells in reserve. However when it does occur, our B cells will have to work harder and become more stressed. Therefore the problem propagates and the chance of developing diabetes is increased.
TXNIP is involved in the exacerbation of the IL-1 pathway and cell apoptosis. Current studies are looking into IL-1 targeting, however new research has shown that TXNIP is a very central player in the stimulation of the IL-1 pathway. Therefore if you remove TXNIP from the equation you will save B-cells from apoptosis and in theory protect the body form developing diabetes. This has been shown by the researchers to occur in mouse models. Consequently this idea is being translated and tested in up coming clinical trails. The hope is that by shutting down TXNIP we will prevent cell stress and hopefully delay or stop the onset of diabetes. However my question is surely TXNIP has a natural role in the body, by shutting it off are we not in danger of loosing its benefits? What do you think about this new development?
S.Packer
