Can Pax4 have a malignant effect on other pancreatic cells?

In the last post, it was made clear that activating the Pax4 gene (Paired Box gene 4) has the beneficial power to transform glucagon-producing alpha cells into insulin-producing beta cells. Like insulin, glucagon is a hormone, but it is different in that it raises blood-glucose levels. The main problem in diabetes is that glucose cannot enter cells because of lack of insulin, so it simply stays in the blood, raising blood-sugar levels. Therefore, it seems that converting glucagon-producing cells into insulin-producing cells is a great leap forward, since insulin removes glucose from the blood and lets it enter body cells. Upon further inspection, this new discovery has another side effect that might not be so fortunate.

The scientific term for the new cells's appearances is that the previous alpha cell now has a beta cell phenotype. In other words, a phenotype is how something looks, or its observable characteristics, the cell now looks like a beta cell and produces insulin like beta cells. However, the research paper shows that this new cell still has traces of galactosidase, something found only in alpha cells. The presence of this indicates that these new beta cells at

one point did produce glucagon.

In 2009, a medical paper was released by several authors (the link is in the title of this post) that gave evidence to the notion that the activation of the Pax4 gene not only drastically decreased glucagon production, but also increased the size of the islets of Langerhans by several times. The image on the above left show a bar graph that illustrates how much larger the islet cells get as well as the ratio of glucagon-insulin production after the Pax4 gene has been turned on. By clicking here, and then in the new page, clicking on the image for a larger view, you can see just how much the size increases. If a small mini-view window shows up, click on the arrow pointing down diagonally at the bottom right-hand corner of the mini-view window. Scroll to the bottom of the image, and you will see a bar graph. The blue segments represent insulin production, and the red represent glucagon production. From left to right, the amount of time increases that the Pax4 gene has been activated. Therefore, it can

clearly be seen that insulin production is taking over, which may

seem like good news at first.

On the other hand, pay attention to the words on the bottom below the bars on the graph. These show the size of the islets of Langerhans, and they are increasing. Initially, they are normally, and then suddenly the it climbs to an enormous 359% increase. This means that each new islet is over 3.5 times larger than before. The news only gets more intriguing. The number then climbs to 682%, and then after some time of decreasing, it peaks at a stunning 709%, or 7 times its original size. More research is in progress, and the Pax4 gene is not going to be discarded because of this evidence. Research is ensuing to find a way to "shut off" or deactivate this gene that could potentially be the seed that finally cures this disease that has stumped scientists for decades. (Image on the right is of a normal pancreatic islet from a mouse. Insulin is stained green, and glucagon is stained a red-orange)