How Do α-Cells Get Reprogrammed?
The researchers concluded that the α-cells were responsible for the new insulin-producing β-cells that were being created, but this leaves open the big question of how. The study does not answer this question, but does offer a potential explanation, and does open the door to further research in this area.
α- and β-cells might seem functionally opposite if you just look at their affects– α-cells produce a hormone that raises blood glucose levels, and β-cells produce a hormone that lowers them– but biologically speaking the cells are fairly similar. They share several transcription factors (proteins that bind to certain segments of DNA and help control the flow of genetic information), and have similar means of managing glucose and secreting hormones. These similarities mean that the differences between the two cell types is one of specific gene and protein interaction, rather than one of basic machinery and type.
It is notable, therefore, that in the early days after diphtheria injection, some α-cells begin to express the transcription factor Pdx1. This protein is an insulin promoter– that is, it binds to segments of DNA so that the creation of insulin is increased, and the creation of glucagon is decreased. Pdx1 is a key identifier of β-cells, and is normally not found in α-cells. After all the β-cells were killed off, though, the researchers found not just Pdx1, but several other β-cell transcription factors, expressed in a subset of α-cells.
The researchers postulate, therefore, that the killing of all of the β-cells releases some sort of signal within the pancreas that causes the α-cells to begin the process of reprogramming. First, they allow the expression of β-cell transcription factors; these in turn cause the co-production of glucagon and insulin, until eventually the glucagon production drops off and the new cells produce only insulin, and have all the transcription factors that original β-cells would. This hypothesis is supported by the fact that leaving behind too many original β-cells seems to hinder, rather than help, β-cell regeneration, and also by the existence of the bihormonal cells with the β-cell transcription factors.
Why is this study different? Why do I care? Well, firstly, I am constantly amazed by the plasticity and adaptability of nature. The pancreas regenerates β-cells on its own! Given enough time and respite from auto-immune regression, these mice self-healed from diabetes! I like that idea.
More scientifically speaking, though, the potential for α-cells to serve as a source for new β-cells is a largely unexplored area of research, and opens up new doors for potential Type 1 diabetes cures. One important implication is that if we can solve part 1 of problem of curing diabetes, controlling the immune system’s war on my β-cells, then there are multiple paths to safely regenerate β-cells, without having to contend with possible rejection of implants or foreign cells.
There are many questions left unanswered– How exactly do α-cells get reprogrammed? Does this happen in humans, too? Why does the number of β-cells regenerated vary so much from specimen to specimen?– but this is one more step in the right direction. Onward and upward, my beloved scientists and researchers! I’m counting on you; keep up the good work!