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Examining Pancreatic Beta Cell Regeneration Processes

Researchers often use cell cultures and tissue slices to study the function and processes of various cells. One of the challenges of this approach, however, is the viability of these samples. For instance, pancreatic tissue slices typically show significant cell death after less than 24 hours due to poor oxygenation. This means that only short-term studies are possible, using samples while they are most viable and representative of the integrity of the native organ.

But, researchers are looking to change that. In a recent study, scientists altered how human pancreatic slices (HPSs) are cultured and managed to preserve function for 10 days or more. This is significant when it comes to being able to conduct longer-term longitudinal studies. Studies were also conducted on tissue samples from non-transgenic mice.

Traditionally, HPSs are preserved in standard transwell dishes. In this model, tissue is placed on top of a liquid-permeable membrane and surrounded with an air-liquid medium. However, oxygenation begins to decrease within several hours, and signs of anoxia appear. A new approach uses perfluorocarbon (PFC)-based dishes. This model places tissue atop a liquid-impermeable membrane providing direct contact with oxygen. An air-liquid medium also surrounds the slice. A variety of testing shows that PFC-based cultures have improved oxygenation and lower levels of anoxia.

In turn, this allowed scientists to more effectively study pancreatic beta-cell regeneration processes. HPSs retain “near-intact cytoarchitecture” of the organ in its native state in the body. Combined with the longer-term viability of the samples in the PFC-based setting, researchers were able to focus in on how and where beta cells were regenerating. They used HPSs from non-diabetic individuals as well as those with type 2 diabetes to enhance their understanding of how to stimulate this regeneration and improve insulin production.

When samples were left to rest for 24 hours to reduce the impact of stress from slicing and then treated with Bone morphogenetic protein 7 (BMP-7) proteins, scientists found that they showed higher levels of beta-cell regeneration than controls that were not treated with BMP-7. Much of this cell development occurred in regions corresponding to pancreatic ducts. Some new cells emerged from existing beta cells, while others transitioned from alpha to beta cells.

Improved oxygenation methods are changing how scientists are able to interact with HPSs and the types of testing they are able to conduct. According to the study, “Our goal in refining the conditions for the long-term survival of HPS was to allow for the real-time detection and quantification of endocrine cell regeneration.” While more in-depth and extensive studies are needed, these findings may lead the way toward improved understanding of the pathology of pancreatic beta-cell regeneration and new treatment options for individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is committed to supporting these types of advancements and efforts by providing critical funding to early-career scientists pursuing novel, peer-reviewed research related to type 1 diabetes. With adequate funding, scientists are able to bring their ideas to life and contribute to not only greater understanding of the disease, but improved methods and therapies for diagnosing, treating, managing, and eventually curing type 1 diabetes. Learn more about current projects and support these efforts by visiting https://diabetesresearchconnection.org.

 

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Could Advancements in Gene Editing Reverse Type 1 Diabetes?

Gene therapy is not a new approach when it comes to treating type 1 diabetes. Scientists have been experimenting with many different options in order to stimulate the body to once again produce its own insulin and reduce or eliminate the need for insulin injections. However, some of the problems that scientists often encounter when introducing new cells into the body are that patients typically require immunosuppressant drugs which can lead to a variety of complications, the body rejects the cells over time, or the cells stop working. Finding a long-term, effective solution has been challenging.

Scientists are making strides in their efforts, though. A recent study examined the potential of using the gene-editing tool CRISPR to correct genetic mutations and create induced pluripotent stem cells that can be transformed into pancreatic beta cells. In mouse models, after the new cells were injected, mice achieved normoglycemia within a week and maintained this status for at least six months.

This approach has not yet been tested in humans, however, because it comes with its own set of challenges. First, the study was done using cells from patients with Wolfram syndrome, a condition that causes diabetes and deafness. This condition can be pinpointed to a single genetic mutation, whereas type 1 diabetes cannot. Type 1 diabetes has been tied to multiple gene mutations, as well as environmental factors. Gene-editing would have to be personalized for each individual, which could take a lot of time.

In addition, it could take billions of cells to effectively reverse diabetes in a patient, and generating this massive number of cells could take months, so it could end up being a long process to treat even one person. Plus, scientists are not entirely sure where the best place to transplant these cells is yet. They must find the spot where they will be most beneficial and able to carry out their intended purpose.

Another study using CRISPR technology is being conducted by a different group of researchers and is focused on using stem cells from the human cell line rather than from individual patients. This would make it easier to produce mass quantities of cells in a shorter period of time. It also would not require scientists to correct specific genetic mutations. CRISPR would be used to edit cells to prevent them from being attacked and destroyed by the body’s immune system.

A challenge with these approaches is that there are a lot of questions and regulations when it comes to gene-editing and using CRISPR on human subjects. Clinical trials are still in very early stages. Studies involving induced pluripotent stem cells are also relatively new in the United States. There is still a lot of work, research, and testing that needs to be done before gene-editing therapy could potentially be used on humans.

Diabetes Research Connection (DRC) will continue to follow these advancements and what they could mean for future diabetes treatment. DRC supports early-career scientists in contributing valuable discoveries and information of their own to the field by providing critical research funding. All projects funded by the DRC are focused on the prevention, treatment, and cure of type 1 diabetes, as well as minimizing complications and improving the quality of life for individuals living with the disease. Learn more and support these efforts by visiting https://diabetesresearchconnection.org.

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Targeting Stem Cell-Generated Beta Cells for Type 1 Diabetes Treatment

In developing more effective treatment methods for type 1 diabetes, several approaches have targeted the disease at a cellular level. Scientists know that, on the most basic level, the disease stems from the destruction of insulin-producing beta cells. However, they are unsure exactly what causes the body to mistakenly attack and destroy these cells. There have been many studies looking at how to reintroduce or stimulate these beta cells within the body in order to produce insulin naturally, but this is a difficult process and one that is hard to sustain.

A recent study may have found a way to improve the number and quality of beta cells produced for cell replacement therapy. The differentiation of human pluripotent stem cells into targeted beta cells is a long, complex process that can take weeks. Even after the process is finished, there is an assortment of cells that have been produced because not all cells differentiate as desired. In addition, not all beta cells are fully functional.

Researchers found that by adding CD77, a monoclonal antibody, they can better control the differentiation of cells into specific pancreatic progenitors. Having these pancreatic progenitors present at the start of the differentiation process may lead to higher quality beta cells that are more responsive to glucose and have improved insulin secretion abilities. In addition, it may help direct differentiation meaning a more homogenous group of cells is created, which is beneficial for cell replacement therapy. Having more of the desired type of cell can also save time and money.

Being able to better control the differentiation process may improve beta cell replacement therapy options for individuals with type 1 diabetes. Developing ways for the body to once again generate its own insulin and manage blood glucose levels could change the way the disease is managed. This study was a partnership between Helmholtz Zentrum München, the German Center for Diabetes Research (DZD), Technical University of Munich (TUM), and Miltenyi Biotec.

Though not involved with this study, the Diabetes Research Connection stays abreast of the latest advancements in the field and how emerging research may impact the diagnosis, treatment, and management of type 1 diabetes, as well as the search for a cure. As more about the disease is understood, researchers can build on this information. The DRC provides critical funding for early-career scientists whose research is focused on type 1 diabetes. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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Could Vitamin D Help Protect Against Type 1 Diabetes?

One trend that researchers have noticed in type 1 diabetes (T1D) is that individuals with this disease tend to have some level of vitamin D deficiency. This impacts vitamin D receptor (VDR) expression, which may contribute to the development of diabetes.

A recent study found that higher levels of VDR may actually protect insulin-producing pancreatic beta cells and preserve some of their mass and function. They also found that as circulating glucose levels decreased, so did VDR levels. Maintaining a stable level of vitamin D may help counteract the disease.

Researchers are investigating the potential effectiveness of using vitamin D supplements as a prevention and treatment strategy for type 1 diabetes, and it may be beneficial for type 2 diabetes as well. They need to develop a clearer understanding of the negative regulation of VDR in individuals with the disease and how to improve VDR levels to a point where they would be more protective.

This study was conducted on mouse models, so it would need to be tested in humans as well to see if the same findings are true. However, this could be a step toward proactively reducing risk of T1D and protecting insulin-producing beta-cell function and mass. Researchers are continuing to learn more about VDR expression and its relationship to diabetes.

Diabetes Research Connection, though not involved with this study, is committed to supporting early-career scientists pursuing novel research on type 1 diabetes in order to expand the body of knowledge and help prevent or cure the disease in addition to reducing complications and improving quality of life for those living with the disease. Scientists are learning more every day. To support these efforts and find out more about current projects, visit https://diabetesresearchconnection.org.

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Could There Be More than One Form of Type 1 Diabetes?

Researchers know that there are significant differences between type 1 diabetes (T1D) and type 2 diabetes (T2D), but now they are digging a little deeper. When it comes to T1D, the disease may not affect everyone in the same way. According to a recent study, there may be more than one endotype, and a major differentiator could be age of diagnosis.

The study looked at a small sample of 19 children diagnosed with T1D within the past two years and compared age of diagnosis against amount of beta cell destruction and levels of proinsulin and C-peptides. They also compared these ratios in a group of 171 adults with T1D based on their age of diagnosis. Their results showed that children who were diagnosed before the age of 7 had much higher levels of proinsulin-insulin co-localization than those diagnosed after age 13. Individuals between ages 7 and 13 were divided and fell into one group or the other.

The researchers also compared results against CD20Hi and CD20Lo immune profile designations for each participant. Children age 7 or younger tended to be CD20Hi, while those age 13 or older were CD20Lo, and the children in between were aligned with their respective groups based on whether they were CD20Hi or CD20Lo.

These differences in proinsulin and C-peptide concentrations demonstrate a distinction in how individuals are impacted by T1D, leading to at least two separate endotypes. Understanding whether an individual has T1D endotype 1 (T1DE1) or T1D endotype 2 (T1DE2) could enable more targeted and effective treatment of the disease based on how each group responds. Individuals with T1DE1 are identified as having higher levels of beta cell loss, therefore may have more difficulty regulating blood glucose. Those with T1DE2 may retain more beta cells, and determining ways to activate and protect these cells could support improved natural insulin production.

Recognizing that T1D affects people differently is a step in the right direction toward more personalized medicine and targeted therapies. Therapeutic trials could be aimed at groups depending on age of diagnosis and specific endotype in the future as larger studies are conducted to determine the significance of these findings.

Diabetes Research Connection (DRC) is committed to supporting advances in research around type 1 diabetes and provides early-career scientists with critical funding for their studies. Research is focused on preventing and curing type 1 diabetes, minimizing complications, and improving quality of life for those living with the disease. Learn more and support these efforts by visiting https://diabetesresearchconnection.org.

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Advancements in Characterizing Type 1 Diabetes Heterogeneity

No two people with type 1 diabetes are exactly the same. Each experiences disease progression differently, and the genetic and biological factors that impact this process differ as well. This can make understanding how type 1 diabetes initially develops and the risk factors involved more challenging.

A recent study examined islet autoimmunity and heterogeneity across a group of 80 individuals diagnosed with juvenile-onset type 1 diabetes. Some had only been recently diagnosed while others had been living with the disease for many years. The study evaluated immunological, genetic, and clinical differences between individuals in order to create more detailed profiles and stratify findings.

Blood samples were taken and testing conducted to determine T-cell response to various beta cell antigens including GAD65, islet antigen-2 (IA-2), preproinsulin (PPI), and defective ribosomal product of the insulin gene (INS-DRIP). Results show that some individuals were high responders showing T-cell proliferation for all four beta cell antigens, some were intermediate responders showing proliferation to one to three beta cell antigens, and the rest were non-responders who did not show any T-cell proliferation response to the tested beta cell antigens.

In addition, more than 80 percent of participants were categorized as high risk by having an HLA-DR-DQ genotype that is associated with development of type 1 diabetes. High responders also had higher non-HLA genetic risk scores than the other two groups. Another interesting finding was that individuals who had longer disease durations also showed an increase in beta cell-specific T-cell proliferation.

Though a larger study is needed to further build out full immunological heterogeneity and explore the interactions between different variables, this study is a strong starting point. Better understanding the complete profile of individuals with type 1 diabetes and how their body responds to different factors could lead to more individualized treatment to help manage the disease. Researchers can tailor treatment toward which beta cell antigens a person responds to, whether they or not they have high HLA-DR-DQ risk or not, as well as other variables.

The body of knowledge surrounding type 1 diabetes is always growing and improving. This is critical to advance prevention and treatment options. Diabetes Research Connection (DRC) supports early career scientists in pursuing novel research studies in order to continue moving understanding forward. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

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Exploring C-Peptide Persistence in Type 1 Diabetes

In diagnosing diabetes, be it type 1 or type 2, one of the key factors doctors look for is C-peptide levels. Traditionally, scientists have believed that low C-peptide levels indicated type 1 diabetes as the body is unable to produce an adequate supply (if any) of insulin, while higher C-peptide levels were associated with type 2 diabetes as the body made insulin but was unable to effectively use it.

However, a recent study shows that this may not be entirely accurate. In a large cohort study in Scotland, there was a broad range of variability in C-peptide persistence across individuals of different ages and duration of disease. Individuals who were older when diagnosed and were close to age of diagnosis had higher C-peptide levels than those who were adolescents when diagnosed and had been living with the disease for a longer period of time. Scientists believe this may point toward there being multiple genetic networks that impact diabetes risk.

The findings also showed that similar C-peptide levels may be present in individuals with adult-onset type 1 diabetes who did not immediately require insulin treatment as those who were diagnosed with type 2 diabetes. Many people with higher C-peptide levels also have increased amounts of proinsulin, which is a prohormone precursor to insulin. However, the cells do not respond to primary stimuli which could mean that they are in a stunned state. If this is the case, there is a potential that they could recover and once again play an active role in insulin production.

The ratio of proinsulin to C-peptide may also be influenced by genetic risk of diabetes. Both genetics and environmental factors may come into play regarding damage to beta cells and their ability or inability to produce insulin.

This study challenges previous understanding about the differences in type 1 and type 2 diabetes when it comes to diagnosis and treatment. There may be the potential to stimulate pancreatic beta cell function in individuals with type 1 diabetes depending on their levels of proinsulin, insulin, and C-peptide.

Diabetes Research Connection (DRC) is interested to see how this may impact the future of diagnosis and treatment of diabetes. It could certainly lead the way to more in-depth research opportunities, and the DRC provides critical funding to support these types of initiatives. Early career scientists can receive up to $75K from the DRC to pursue novel research projects focused on type 1 diabetes. To learn more, visit http://diabetesresearchconnection.org.

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