Gene Finding Provides New Insights

    Today's blog post has to do with new gene findings which provide new insights into pancreas development and in helping search for a cure to type 1 diabetes. For those with diabetes, glucose can't be used for energy, so it builds up in someone's bloodstream and causes serious health problems. Luckily, there is a peptide hormone called 'Insulin' that is produced by beta cells of the pancreatic islets which are encoded by the insulin gene in humans. Recently though, scientists found a gene which is essential for making the pancreas; and this gene is not found in almost all animals, except for chimpanzees, gorillas, and a few other types of monkeys. 

    A study was done and that is when the gene, which is called ZNF808 was found. By finding this gene during the study, it was able to show how different humans and animals are when it comes to research, and it really showed the importance of studies on the human pancreas. By studying the pancreas, we would be able to find new treatment for diabetes, and also figure out why the human pancreas is different in how it looks and develops compared to animals. After studying the ZNF808 gene it was found that it is a part of a family of evolved proteins which are in regions of DNA that they consider junk DNA. After recent studies it shows that this region of DNA where ZNF808 is, is actually an important role in human development. 

    Now that the DNA region in which ZNF808 was found is being studied, we understand that there are hundreds of genes which are like ZNF808 that will be able to help in overall human health. In the lab it was studied on the effect of ZNF808 loss while using stem cells; and it was found that ZNF808 plays a big role in important functions during early human development when our cells have to decide whether they want to become a pancreas or a liver. With this finding it is now known that this could be used to manipulate stem cells so that they produce beta cells which will be able to produce insulin on their own. If that works out we will be faced with finding a cure for type 1 diabetes.

Main Source:

Gene finding provides new insights into pancreas development and helps search for type 1 diabetes cure (medicalxpress.com)

Other Sources:

The Relationship Between Insulin And Glucose | DiabetesTalk.Net

Association Between Diabetes and ZRANB3 Gene

The journal Nature Communications published the largest genomic study of type 2 diabetes (T2D) in sub-Saharan Africans, in which they analyzed nearly 18 million autosomal SNPs in 5,231 individuals from Nigeria, Ghana, and Kenya (Nature, 2019). Researchers found that there was a connection between diabetes and genome-wide significant locus: ZRANB3 gene. They confirmed the ZRANB3 gene, might influence weakness to the T2D in sub-Saharan African populations. They studied its effects on the zebrafish pancreas; "the pancreas is one of the key organs involved in T2D because their β-cells release insulin as a response to rising glucose in the bloodstream" (NIH, 2019).

CRISPR, a gene-editing tool was used to make the ZRANB3 gene nonfunctional in zebrafish. This is called a 'knockout'. They also reduced the expression of the ZRANB3 gene in a different sample of zebrafish. Researchers observed β-cells were reduced numbers in the developing zebrafish embryo (Nature, 2019). They concluded that when the ZRANB3 gene was inactive, pancreatic β-cells were being destroyed. They conducted a similar experiment using mice and found similar results. They proposed an excellent question on this finding: will it help to predict whether the presence of ZRANB3 in an individual with T2D require insulin early in the course of its treatment? This is significant because it could save the destruction of β-cells over time.  They also believed since ZRANB3 in T2D was discovered in African populations, the same gene might have same influence in other populations. I think this experiment was executed brilliantly considering they analyzed so much data before concluding. I think it is amazing that they want to continue the research with different pollutions and hope to find a similar association between T2D and ZRANB3 gene. 

References: 

NIH/National Human Genome Research Institute. (2019, July 19). Largest genomic study on type 2 diabetes in sub-Saharan African populations. ScienceDaily. Retrieved October 18, 2019 from www.sciencedaily.com/releases/2019/07/190719080212.htm

ZRANB3 is an African-specific type 2 diabetes locus associated with beta-cell mass and insulin response. (2019, July 19). Retrieved October 18, 2019, from https://www.nature.com/articles/s41467-019-10967-7#article-info.

Insulin Injections are about to be a thing of the Past

Type 1 diabetes is an autoimmune disease that causes the body to kill off all of its pancreatic beta cells.  A new diabetes treatment can potentially eliminate the need to inject insulin, thanks to a cell-based treatment. Instead of insulin injections, a new diabetes treatment would include only having to get an implant. This implant would need to be replaced only three times a year. In this new form of therapy,  a capsule of genetically engineered cells would be implanted under the skin. This capsule would release the needed amount of insulin just as an injection would.

In an experiment to test the safety, diabetic mice were treated with these cells and ended up having normal blood sugar levels for several weeks. Scientists are working hard to obtain a clinical trial license in order to test this technology in patients. The treatment would be able to work with type 1and type 2 diabetes patients and scientists are hopeful to start testing in patients in little as 2 years. A lead researcher at the ETH university in Basel, Martin Fussenegger, states, “By 2040, every tenth human on the planet will suffer from some kind of diabetes”. Fussenegger’s team re-engineered human kidney cells, or HEK cells to perform the same function that the pancreas performs. It introduced two cells: one to make them sensitive to glucose levels and another to instruct the cell to pump out insulin when glucose levels exceeded a threshold. Overall, in the study, the engineered HEK cells actually outperformed the normal pancreatic cells. The ability of them to regulate blood sugar in mice worked very well. If this same procedure can happen for humans, the cells would not need to be genetically matched to the patient. The frozen capsules could be manufactured on an industrial scale. This technique is said to be in the market within a decade.I think this would be an amazing advancement, considering that individuals would not need to inject insulin several times a day. 

A Contradiction to the "Lifestyle" Disease

    Recently published in Nature Genetics, Dr. Sylvie Lesage has discovered that a common genetic defect in beta cells may be the true cause of both Type 1 and Type 2 Diabetes.  Diabetes is often labeled the "lifestyle" disease due to the fact that Type 2 Diabetes is linked to obesity and poor health habits which cause a metabolic dysfunction of the liver. Type 1 Diabetes however,  is caused at a young age by an autoimmune destruction of the pancreatic beta cells which produce insulin. With thanks to the new discoveries it is evident that genetics plays a large role in whether a person develops the disease or not.
    Dr. Lesage states that some people have beta cells that are tough and can handle stress very well and others have the opposite characteristics. Those who have very tough and robust beta cells will remain healthy even if they suffer from an autoimmunity or metabolic disfunction of the liver. It can be said that these people are rather lucky. Whereas the unlucky people with weaker beta cells will develop the disease if they suffer from an autoimmunity or dysfunction of the liver. This discovery was made possible due to experiments that were done on mice by Dr. Adrian Liston which concluded with the information that is stated above.

    What can be taken from this newfound information is that there is a new factor that must be taken into account when studying Diabetes and the susceptibility that people have to developing this debilitating disease. I can predict that in the future a routine test to measure beta cells will be given to patients in order for doctors to be able to properly advise their patients on how to take care of their bodies. Those patients that have tough beta cells will be advised to continue to live a healthy lifestyle but will not be at high risk of developing Diabetes. Those patients that have weaker beta cells will be given the proper precautions and informed of their higher susceptibility to developing the disease. With this testing it will hopefully be possible to prevent this disease from continuing to become more prominent.