Levi Myers

BIO 4500

Pathology of Diabetes

The first time I took ideas from two reading places was when I made the connection between epigenetics and the disease state of diabetes from class reading. In the epigenetic reading I learned a few key concepts that I was able to connect with diabetes that helped me to understand the disease a bit better. The first of these was how histone modification is responsible for the different cell products available in the many cell types. These histone modifications alter how tightly the DNA is bound. The tighter the nucleosomes are bundled the less transcriptionally active the segment of DNA will be. I then applied this concept to a few of the common problem mechanisms involved with diabetes. First was how pancreatic beta cells produce insulin. These cells have segments of the DNA that code for the hormone insulin that is transcriptionally active. One of the problems that is common in diabetes is that the beta cells get overworked and cease to produce the needed amount of insulin. The other location where gene control would be important is in the expression of the glut transporters. In a normal cell insulin binds and causes the glut transporters to be inserted into the membrane of the cell so the glucose can be absorbed. From my reading I learned that one of the mechanisms of insulin resistance is that even thought there is insulin in the blood stream when it binds to the insulin receptor there is not enough of the glut transporter to absorb the glucose in the blood stream. This leads to a few of the common symptoms of diabetes including hypersinsulemia, and hyperglycemia. I connected this with epigenetics, as there must be a connection to the diabetic disease state and how less glut transporter is produced. From this I also learned that all disease could be taken down to the cellular levels.

For my second place where I was able to make connection through my reading I was studying advanced glycolation products and pathology of diabetes. These products are formed from the high levels of glucose in the blood. Also important is the length of time the blood glucose is elevated. When this combination of extended high glucose levels is present it leads to glycolated products. One of these is hemoglobin. In this case there are glucose molecules that bind to one of the subunits on hemoglobin. I had previously known of these products but was not able to make the connection to how they were harmful. From my reading there were two ideas that I learned that I had never heard of. The first was that AGEs have a specific receptor that they bind to called RAGE. This receptor when bound leads to the expression of growth factors and other harmful products that increase the coagulation of endothelial cells and lead to the deposition of basement membrane material. I also learned about how glucose bind to different types of collagen and this leads to interactions with proteins in the blood and lead to much of the vascular abnormalities see in patients with diabetes such as atherosclerosis, retinopathy, and decreased elasticity of vessels. This specifically applied to bigger vessels and how by this crosslinking of collagen the vessel walls become less elastic. When this happens the vessels are less likely to be able to accommodate high-pressure situations. This leads to small tears in the lining of the vessel and lead to atherosclerosis and other vasculature problem. Common also in people that type 2 diabetes is hyperlipidemia. I was able to connect this with the RAGE receptor and how it releases factors that lead to increased cell adhesion. This in combination with these tears in vessel walls leads to the deposition of fat cells at the site of injury. This leads to the buildup of macrophages and other cells that slowly lead to the occlusion of smaller vessels or in sever cases an unstable angina. These can break off from the vessel wall and turn into a pulmonary embolus or even stroke based on where the embolus lands. Mostly I was able to connect a bunch of different diseases that I had learned with understanding a few of the physiological mechanisms regarding diabetes.

            For my third place where I was able to connect multiple ideas from my reading I connected with what other things have been rising at the same time as diabetes specifically the last 50 years.  There were a few things that came to mind. The first thing was as there was an increase in diabetes there was an increase in the marketability and consumption of fast food in the United States. This is by no means causation, however it is an interesting correlation. This has led to an increased availability of these high calorie foods and also the continued development of the idea that time is money. . The second is how this disease has grown in concert with music and technology. These things have tended to get more cerebral as time progresses and there is a turning into the mind that I find to be troubling. While reading an article I came across the term screen time. This was being used in relation to the total time that was spent by an individual on anything with a screen. This value has also been increasing along with the diabetes epidemic.

            In all I was able to learn a lot from my reading and was able to connect more than I thought that I would be able to.