DRC & Research News

This page shares the latest news in T1D research and DRC’s community.

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Improved Beta Cell Function of Transplanted Islet Cells in T1D

One of the major challenges of using transplanted islet cells in the treatment of type 1 diabetes is cell death. Due to cellular stressors, poor oxygenation or vascularization, autoimmune response, and other factors, not all transplanted cells survive, and this can make treatment less effective. The body needs functional insulin-producing islet cells in order to effectively regulate blood sugar levels.

A recent study found that coculturing allogeneic islet beta cells with mesenchymal stromal cells (MSCs) may improve not only cell survival, but function as well. After donor cells are procured, they must be cultured and tested before being transplanted. This can generate significant cellular stress including hypoxia or low oxygenation, which can in turn lead to cell death. However, researchers found that MSCs support islet cells during this culture period by improving oxygenation and insulin secretion.

They also found that in response to these stressors, MSCs actually initiate mitochondria transfer to the islet beta cells.  This may improve mitochondrial ATP generation which plays an integral role in controlling insulin secretion. As a result, as glucose levels around the beta cells increased, so did their production and secretion of insulin.

Researchers experimented with this coculturing process with both mouse cells and human cells and found that human cells have a greater response and higher level of MSC-mediated mitochondria transfer that occurs. Though more extensive testing is necessary, these results show that MSCs may be an essential part of clinical islet transplantation and improved efficacy of beta cell function in treating individuals with type 1 diabetes.

Diabetes Research Connection (DRC) is interested to see how this study evolves moving forward and what it may mean for future therapeutic treatments for the disease. The DRC, though not involved in this study, provides critical funding for early career scientists pursuing novel, peer-reviewed research projects for type 1 diabetes. Click to learn more about current projects and provide support.

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T1D Vaccine

Type 1 Diabetes Vaccine Shows Positive Results

In an effort to prevent or delay the onset of type 1 diabetes, researchers have been striving to create an effective vaccine. One of the challenges is that there are many different subgroups of type 1 diabetes, meaning not all patients respond the same. A recent study found that patients who had a specific human leukocyte antigen (HLA) showed a “positive and statistically significant dose-dependent treatment response” to the Diamyd vaccine, especially when given four doses rather than two.

Compared to patients who received a placebo, those who received a higher number of doses of the Diamyd vaccine had a “statistically significant treatment effect of approximately 60%” within 15 months. These findings may help to advance the development of antigen-specific immunotherapy options for individuals with type 1 diabetes leading to improved treatment or management of the disease.

Diabetes Research Connection (DRC) is interested to see how this vaccine continues to evolve moving forward and what it could mean for the prevention of type 1 diabetes in the future. Though not involved with this study, the DRC provides early career scientists with funding necessary to conduct novel, peer-reviewed research projects around type 1 diabetes in an effort to improve understanding, prevention, treatment, and management of the disease. To learn more or donate to a current project, visit https://diabetesresearchconnection.org.

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Diabetes Researching

Improved Protection for Transplanted Stem Cell-Derived Islets

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. To learn more about current DRC-funded projects or support these efforts, visit https://diabetesresearchconnection.org.

 

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Diabetes Researching

Exploring Why the Immune System May Attack Insulin-Producing Beta Cells

Insulin-producing beta cells are essential for effective blood sugar control. However, in individuals with type 1 diabetes, these cells are mistakenly destroyed by the immune system. That means exogenous insulin must be used instead to manage blood sugar. For years, scientists have been researching ways to replace or reproduce these islet cells. Two of the most common challenges faced, however, have been the need for long-term immunosuppression to protect transplanted cells from rejection, and limited availability of donor cells.

A recent study found that an improved source of encapsulation may protect islet cells from an immune response without decreasing their ability to secrete insulin. By using a conformal coating that is only a few tens of micrometers thick (as opposed to hundreds of micrometers thick), not only could insulin flow more freely through the encapsulation, so could oxygen, nutrients, and glucose as well. Yet larger immune cells were still unable to penetrate the barrier. In addition, the thinner coating allowed for more cells to be contained in a smaller space, and the capsule could be implanted in a wider range of locations so long as there was strong vascular function.

The encapsulated cells were implanted in NOD-scid mice and compared with non-coated stem cells as well as human islets. There were no statistically significant differences in performance of the cells and their ability to regulate glucose levels. The mice all showed a reversal in diabetes with the transplanted cells and returned to hyperglycemia once the cells were explanted.

The use of a microencapsulation method allows for more variability in placement of transplanted cells and helps protects against hypoxia-induced islet death and cell rejection. Furthermore, the thinner coating enabled islets to obtain better oxygenation because they are closer to blood vessels. It also allowed insulin to be secreted more quickly because it flowed more freely through the barrier.

One drawback that researchers noted was that encapsulated islets are unable to shed dead cells because they are contained within the capsule and have a lower absolute quantity of insulin secretion when compared to non-coated stem cell-derived islets.

Through this study, the researchers concluded that, “CC (conformal-coated) mouse islets can reverse diabetes long-term in a fully MHC-mismatched model.” While additional research is necessary to explore the effectiveness of this process in humans, it is a step in the right direction toward one day potentially curing type 1 diabetes.

Though not involved with this study, Diabetes Research Connection (DRC) stays abreast of the latest advancements in the field and provides critical funding to early career scientists pursuing novel research studies for type 1 diabetes. It is through these types of projects that researchers are able to improve quality of life for individuals living with the disease and move closer to finding a cure. Click to learn more about current projects and provide support.

 

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GABA Hormone

Understanding the Impact of GABA on Insulin Secretion and Regulation

In order to manage blood glucose levels, pancreatic beta cells release insulin in pulses. These bursts of insulin help the body to regulate and stabilize blood sugar. In individuals with type 1 diabetes, however, the pancreatic beta cells that normally secrete insulin are mistakenly destroyed by the body. This leaves the body unable to effectively regulate blood sugar on its own. Understanding the interaction between insulin-producing beta cells and other processes in the body may help researchers improve treatment and prevention options when it comes to diabetes.

A recent study examined the different roles gamma amino-butyric acid (GABA) plays in cell activity. In the brain, GABA is released from nerve cell vesicles each time a nerve impulse occurs. The GABA prepares cells for subsequent impulses by working as a calming agent. Researchers previously believed that this process worked in much the same way in the pancreas.

However, in the pancreas, GABA is evenly distributed throughout the beta cells rather than contained within small vesicles, and it is transported via the volume regulatory anion channel. This is the same channel that helps stabilize pressure inside and outside of cells so that they maintain their shape. Furthermore, research showed that GABA is released in a similar pattern and frequency as pulsatile in vivo insulin secretion. Just like in the brain, GABA plays an integral role in preparing and calming cells to make them more receptive to subsequent insulin pulses.

Scientists are interested in learning more about how GABA signaling can support the regulation of insulin secretion and potentially protect cells from autoimmune activity. This opens new doors for biomedical research that has the ability to impact diabetes care.

It is encouraging to see different types of researchers all coming together and learning from and building upon one another’s work in order to advance understanding, prevention, and treatment of various diseases, including diabetes.

Diabetes Research Connection stays abreast of the latest discoveries in the field and supports early career scientists in contributing to this body of work by providing critical funding for their projects. It is essential that scientists have the resources to pursue novel research in order to develop improved prevention, treatment, and management options for type 1 diabetes. Learn more and support current projects by visiting https://diabetesresearchconnection.org.

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OUR PROJECTS

See our approved research projects and campaigns.

Role of the integrated stress response in type 1 diabetes pathogenesis
In individuals with type 1 diabetes (T1D), the insulin-producing beta cells are spontaneously destroyed by their own immune system. The trigger that provokes the immune system to destroy the beta cells is unknown. However, accumulating evidence suggest that signals are perhaps first sent out by the stressed beta cells that eventually attracts the immune cells. Stressed cells adapt different stress mitigation systems as an adaptive response. However, when these adaptive responses go awry, it results in cell death. One of the stress response mechanisms, namely the integrated stress response (ISR) is activated under a variety of stressful stimuli to promote cell survival. However, when ISR is chronically activated, it can be damaging to the cells and can lead to cell death. The role of the ISR in the context of T1D is unknown. Therefore, in this DRC funded study, we propose to study the ISR in the beta cells to determine its role in propagating T1D.
Wearable Skin Fluorescence Imaging Patch for the Detection of Blood Glucose Level on an Engineered Skin Platform
zhang
A Potential Second Cure for T1D by Re-Educating the Patient’s Immune System
L Ferreira
Validating the Hypothesis to Cure T1D by Eliminating the Rejection of Cells From Another Person by Farming Beta Cells From a Patient’s Own Stem Cells
Han Zhu
Taming a Particularly Lethal Category of Cells May Reduce/Eliminate the Onset of T1D
JRDwyer 2022 Lab 1
Can the Inhibition of One Specific Body Gene Prevent Type 1 Diabetes?
Melanie
Is Cholesterol Exacerbating T1D by Reducing the Functionality and Regeneration Ability of Residual Beta Cells?
Regeneration Ability of Residual Beta Cells
A Call to Question… Is T1D Caused by Dysfunctionality of Two Pancreatic Cells (β and α)?
Xin Tong
Novel therapy initiative with potential path to preventing T1D by targeting TWO components of T1D development (autoimmune response and beta-cell survival)
flavia pecanha