Alpha to Beta: Modifying Chromosomes to Fight Diabetes

Recently, researchers have reported that they may have discovered a new technique to treat diabetes mellitus (commonly just called diabetes, although there are several other forms of the disease). Diabetes is a disease of the endocrine system, the system of the body that is responsible for the production of hormones. Hormones help regulate body activities such as response to stress, metabolic rate, and water retention. In the case of diabetes, the disease is to an inability of the pancreas to produce insulin, one of the hormones involved in the regulation of blood sugar levels.

There are two primary forms of diabetes:

  1. Type 1 diabetes  – this occurs when the pancreas does not produce any insulin.
  2. Type 2 diabetes – this occurs when either the body does not produce enough insulin, or when the cells of the body do not respond correctly to insulin in the blood. This is the most common form of diabetes.

The job of insulin is to lower blood glucose levels. Insulin is usually released into the blood following a meal, when carbohydrates in the food are broken down into glucose. Insulin is produced by cells in the pancreas called beta cells.  In type I diabetes, these cells are often destroyed by an autoimmune reaction, so the body lacks the ability to produce insulin. In type II diabetes, insulin is produced, but its effects are largely ignored by the body. This type of diabetes often occurs in people with high amounts of body fat, since fat tissue (called adipose tissue) does not respond well to insulin.  Another type of cell in the pancreas is the alpha cells. Alpha cells produce glucagon, which acts to raise blood glucose levels.

Treatment for diabetes most often includes injections of insulin and regulation of the diet. While effective, these treatments target the symptoms of diabetes, they do not cure the disease. However,  researchers at the Perelman School of Medicine, University of Pennsylvania have proposed a possible mechanism to increase insulin production by converting some of the alpha cells to beta cells.

In animals, all of the cells of an organism are derived from a single cell that formed when the egg and sperm cell fused. Because of this, every cell of the body has basically the same genetic information, which means that , technically at least, any cell in the body has the full library of instructions to be any other cell in the body.

What distinguishes one type of cell from another? Basically it is the regulation of which set of genes are expressed in the cell. There are many different ways to regulate gene expression – the ones most often discussed in biology classes involve regulation of the process of protein synthesis (transcription and translation)

But increasingly, geneticists are recognizing that other factors, including the way that the DNA is packaged within the cell. Packaging is important to a cell. Within each cell are several meters of DNA. in order to make this DNA fit inside the nucleus of a cell, it must be compacted. As shown in the diagram below, this is a multistep process:

chromosomes

Compacting the DNA. From Mader/Windelspecht Biology 11e, used by permission

The researchers  focused on one of the early stages of this process, when the DNA is wrapped around special proteins called histones.

histones

Histones and DNA, from Mader/Windelspecht Biology 11e, used by permission.

When the DNA is wrapped around a histone, it forms a structure called a nucleosome. In most cases, DNA within the nucleosome is inaccessible by the cellular machinery responsible for gene expression, so any genes in this area are basically off. The placement histones  does not appear to be random, it is controlled by a signalling system called methylation. What the researchers at the University of Pennsylvania discovered is that they were able to alter the activity of histones in the alpha cells within the pancreas. This caused a change in the expression of certain genes within the alpha cells. When this occurred, the alpha cells started to produce insulin – in effect, they started to act like beta cells.

What is interesting about this study is that the reprogramming of alpha cells potentially may solve two problems for diabetics. Not only do diabetics not produce enough insulin (due to problems with their beta cells), but they often also over-produce glucagon, the hormone that is responsible for raising blood glucose levels. Since glucagon is made by the alpha cells, it is possible that converting alpha cells to beta cells might also reduce the release of glucagon, which with further reduce blood glucose levels. While additional studies still need to be performed, it may one day be possible to treat diabetes by altering the expression of genes within the pancreas, thus providing the organ with the opportunity to produce insulin. In the case of type I diabetes, this might restore some of function to the pancreas, and for type II diabetes, the increase may allow the pancreas to better control blood glucose levels.

 

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