insulin-producing beta cells - Diabetes Research Connection

Diabetes Research News
July 15, 2020

Could Benefits of Early Screening for Type 1 Diabetes Outweigh Costs?

Advances in science have improved the ability to identify warning signs for type 1 diabetes (T1D) early on. For instance, scientists can detect the destruction of insulin-producing beta cells before noticeable signs of diabetes emerge or conditions such as diabetic ketoacidosis (DKA) occur. They have also determined other key changes and factors that may put an individual at increased risk.

A recent study found that conducting health screenings on children can increase awareness regarding their risk of developing T1D, help prevent DKA occurrences, and encourage individuals to take better care of their health to reduce complications and impact of the disease.

Researchers at the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine created the Autoimmunity Screening for Kids (ASK) study to determine if this type of health screening is beneficial. While it can be costly to conduct widespread screenings for children between the ages of 1 and 17, they found that there are a host of benefits such as those mentioned above. In addition, the long-term cost savings can quickly make up for screening expenses because when individuals know their risk and learn how to better manage their T1D, it can reduce complications and associated healthcare costs.

Now they are looking at how to effectively implement screenings, what the practice would look like, what the age schedule for screenings should be, and who would benefit most. Early detection can play an integral role in managing T1D and improving quality (and quantity) of life.

Diabetes research occurs at all stages of the disease, from the time patients are pre-symptomatic to those with the most serious complications. It covers everything from screenings to closed-loop systems for treatment to understanding the cellular and molecular impact of the disease. Diabetes Research Connection is committed to supporting a wide range of T1D research by providing critical funding to early-career scientists. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

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Diabetes Research News
June 19, 2020

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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Diabetes Research News
May 21, 2020

Generating Pancreatic Islet Organoids to Treat Type 1 Diabetes

In individuals with type 1 diabetes, the immune system mistakenly attacks and destroys insulin-producing beta cells. Without a naturally occurring supply of insulin to manage glucose, blood-glucose levels can quickly spiral out of control leading to hypo- or hyperglycemia. If left untreated, this can become potentially fatal.

A recent study found a way to generate an abundance of pancreatic islet organoids that are glucose-responsive and insulin-secreting. As such, they can help with management and potential reversal of type 1 diabetes. Researchers identified a cluster of protein C receptor positive (Procr⁺) cells in the pancreas of adult mice. These cells have the ability to differentiate into alpha, beta, omega, and pancreatic polypeptide (PP) cells, with beta cells being the most abundant.

The Procr⁺ islet cells can then be cultured to generate a multitude of islet-like organoids. When the organoids were then be transplanted into adult diabetic mice, they were found to reverse type 1 diabetes. More research is necessary to determine if human pancreatic islets contain these same Procr⁺ endocrine progenitors and a similar process could be used to treat type 1 diabetes in humans.

As scientists delve deeper into the cellular impact of the disease and how different cells respond and can be manipulated, it opens new doors to potential treatments or cures for type 1 diabetes. Though not involved in this study, this is the type of cutting-edge research that the Diabetes Research Connection (DRC) is committed to supporting. Early-career scientists can receive up to $50,000 in funding through DRC for novel, peer-reviewed research aimed at preventing and curing type 1 diabetes, minimizing complications, and improving the quality of life for individuals living with the disease. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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Diabetes Research News
May 19, 2020

Could Insulin-Producing Beta Cells Play a Role in Triggering Onset of Type 1 Diabetes?

Researchers know that type 1 diabetes (T1D) occurs when the immune system mistakenly attacks and destroys insulin-producing beta cells. This leaves the body unable to self-regulate blood glucose levels because it produces little or no insulin on its own. What scientists have been striving to understand is what causes the body to destroy these cells in the first place.

A recent study found that the beta cells themselves may play a role in signaling the attack. The insulin-producing cells may be sending out signals that increase M1 macrophages that cause inflammation and the resulting cell destruction. The M2 macrophages that reduce inflammation and help repair tissue are not as heavily expressed.

The researchers looked specifically at Ca2+-independent phospholipase A2beta (iPLA2beta) enzymes and the resulting iPLA2beta-derived lipids (idles) and how they are activated by beta cells. The idols either stimulate M1 macrophages or M2 macrophages depending on the active signaling pathways.

The study involved two sets of mice – one group that had no iPLA2beta expression (knockout mice), and one group with overexpression of iPLA2beta. Researchers found that even when M1 macrophage activation was induced, the knockout mice experienced an increase in M2 macrophages and a reduced inflammatory state. The mice that had overexpression of iPLA2beta, on the other hand, experience an increase in M1 macrophages and inflammatory eicosanoids.

According to Sasanka Ramanadham, Ph.D., research co-lead, “To our knowledge, this is the first demonstration of lipid signaling generated by beta cells having an impact on an immune cell that elicits inflammatory consequences. We think lipids generated by beta cells can cause the cells’ own death.”

As scientists continue to learn more about lipid signaling and the potential role it plays in the development of type 1 diabetes, this could lead to improved methods of delaying or preventing onset or progression of the disease. This is yet another approach that researchers are taking to understand as much as they can about how and why T1D develops and how to better manage the disease.

It is this type of research that opens doors to advancements toward preventing or curing type 1 diabetes. Diabetes Research Connection (DRC) supports early-career scientists pursuing novel, peer-reviewed research studies focused on improving diagnosis, treatment, and prevention of T1D as well as improving quality of life for individuals living with the disease and one day finding a cure. Ensuring researchers receive necessary funding for their projects is critical. To learn more about current projects and support these efforts, visit https://diabetesresearchconnection.org.

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Diabetes Research News
May 14, 2020

Redifferentiating Beta Cells to Treat Type 1 Diabetes

All cells serve a specific purpose, and each one plays an integral role in the function and survival of the human body. However, in individuals with type 1 diabetes, insulin-producing beta cells are destroyed leaving the body unable to self-manage glucose levels. Scientists have been trying to determine exactly why this occurs, and how to stop, prevent, or reverse it for years. Each day they learn a little more.

A recent study out of Germany examines dedifferentiation of beta cells as a potential cause for type 1 diabetes. Researchers believe that insulin-producing beta cells may lose their identity, which in turns causes a regression in function. They sought to target the affected cells using diabetic mouse models to see if they could redifferentiate the beta cells back to normal function, or at least preserve existing function if regression is caught early.

To do this, they invoked diabetes in mice using streptozotocin but left some functional beta cells. Then, they administered a combination of Glucagon-like peptide-1 (GLP-1) and estrogen in conjunction with long-acting insulin. The drug was directed to the dedifferentiated beta cells, and results showed that this combination treatment helped to “normalize glycemia, glucose tolerance, to increase pancreatic insulin content and to increase the number of beta cells.” They also found that when GLP-1/estrogen was used together, rather than each substance on its own, human beta cells also showed improved function.

The mice in the study showed no signs of systemic toxicity even when high doses of the drug were administered. This could help to ease the way when the treatment is ready to be used in human trials. Researchers want to further explore whether this treatment could be used as a form of regenerative therapy to redifferentiate dedifferentiated beta cells and stimulate insulin production. If type 1 diabetes was detected early on, the therapy could potentially be used to slow or stop cell regression.

This study could change the way that some researchers approach their work and inspire new studies aimed at treating or curing type 1 diabetes. Diabetes Research Connection (DRC) supports early-career scientists in pursuing this type of work by providing necessary financial resources. With proper funding, scientists can move forward with their projects and improve not only understanding of the disease, but also treatment options. The goal is to one day discover a cure. To learn more about current projects and how to help, visit https://diabetesresearchconnection.org.

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Diabetes Research News
April 23, 2020

Exploring the Impact of Environment on Type 1 Diabetes Risk

While researchers know that type 1 diabetes is caused by the destruction of insulin-producing beta cells, what they are still uncertain about are the exact causes of this process. They know that genetics play a role, yet there is not a single gene responsible for the disease; there are several genes that are believed to contribute. Furthermore, they are not convinced that the disease is entirely genetic, and have reason to believe that environmental factors are to blame as well. But once again, there is not a single environmental risk that has a significantly greater impact than others.

A recent study examined several environmental risk factors such as “air pollution, diet, childhood obesity, the duration of breastfeeding, the introduction of cow’s milk, infections, and many others” and yet researchers still do not have any definitive answers. What they do know is that the incidence of type 1 diabetes has increased over the past 30 years by 3 percent year over year, and this change is too significant to be caused by genetics alone.

Using a variety of modeling, they evaluated the impact of specific environmental factors over time. But the simulated data did not pinpoint one factor that stood out above the others and had a stronger impact on diabetes risk. It is likely that a combination of environmental factors is at play in conjunction with genetic risk. More research is needed to further investigate potential risks and protective factors when it comes to type 1 diabetes.

These findings may inspire other researchers to dig more deeply into environmental factors and their impact on disease development and progression. Diabetes Research Connection (DRC), though not involved with this study, provides critical funding for early-career scientists to pursue novel research studies related to type 1 diabetes to enhance understanding as well as prevention, treatment, and management of the disease. The goal is ultimately to find a cure. Learn more about current projects and how to help by visiting https://diabetesresearchconnection.org.

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Diabetes Research News
April 14, 2020

Advances in Therapeutic Treatment for Type 1 Diabetes without Immune Suppression

One approach that researchers have been exploring to treat type 1 diabetes is cell therapy. By introducing new insulin-producing beta cells or other types of cells, scientists strive to support the body in once again producing its own insulin. A common challenge with this technique is that it often has limited results as the body once again attacks the cells, or they slowly lose function on their own. In addition, cell therapy typically requires immune suppression which can put individuals at risk for other complications.

However, in a recent study, researchers tested a new method of transplanting therapeutic cells by using a retrievable device with a silicone reservoir. The cells are further protected by a porous polymeric membrane that allows macrophages to enter the device without destroying the transplanted cells, or that prevents them from entering at all.

When tested in immunocompetent mice, the device supported normoglycemia for more than 75 days without the need for immunosuppression. The transplanted cells were able to effectively produce erythropoietin, which in turn improves oxygen supply to the body, and also generates insulin to manage blood sugar levels.

This is a notable step forward in improving cell therapy for the treatment of type 1 diabetes. More research and testing are required to determine how this process translates into human models. Researchers have been trying to limit or eliminate the need for immune suppression while transplanting healthy pancreatic, islet, and stem cells into the body to control blood glucose levels.

Dan Anderson, Ph.D., a member of the Diabetes Research Connection (DRC) Scientific Review Committee, is the senior author of the article published regarding these findings. DRC is excited to see where these advances may lead and what it could mean for the future of cell transplantation techniques and cell therapy for type 1 diabetes. The organization provides critical funding for a wide range of projects related to improving diagnosis, treatment, and prevention of the disease. Learn more about current studies and how to support these efforts by visiting https://diabetesresearchconnection.org.

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Diabetes Research News
February 19, 2020

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 Research News
December 9, 2019

Expanding Type 1 Diabetes Research Through Marmoset Models

It is not uncommon for researchers to use animal models for initial research before transitioning to human clinical trials. Many animals’ systems are biologically similar in nature to humans and respond in similar ways to various diseases and medications. Often mouse models are used for diabetes research, but other species such as nonhuman primates (NHP) are also advantageous. While various types of monkeys and baboons have been used to study diabetes pathogenesis and treatment, there was previously not a marmoset model.

In a recent study, researchers successfully induced type 1 diabetes mellitus in marmosets. They conducted a partial pancreatectomy and administered streptozotocin (STZ) to decrease and destroy insulin-producing beta cells. This led to the marmosets having higher sustained blood glucose levels (above 200 mg/dL) and the inability to manage their condition through natural insulin production. Instead, they were injected with exogenous human insulin which brought their glucose levels back into the target range. Researchers found that they had a high sensitivity to human insulin making them a valuable NHP model.

Multiple glucose and insulin tolerance tests were conducted to determine how the diabetic marmosets responded compared to normal marmosets and whether they would be suitable candidates for future testing regarding islet transplantation. Continuous glucose monitors (CGM) were used to compare normal marmosets with diabetic marmosets as well, further showing that diabetic marmosets had consistently higher blood glucose levels, especially following meals, much like humans with type 1 diabetes.

While additional research is necessary, researchers believe that marmoset models could play an integral role in type 1 diabetes research and the advancement of preclinical testing. They were able to effectively induce diabetes in the marmosets and control it using human insulin, so the next step would be to move to cell transplantation trials. Eventually these transplant models may translate to human clinical trials and enhance diabetes treatment options.

It is these types of studies and use of animal models that help to advance scientists’ understanding and treatment of type 1 diabetes and allow them to work toward a cure. Diabetes Research Connection (DRC) is interested to see how marmoset models will influence the future of diabetes care.

DRC is committed to supporting early career scientists in pursuing novel, peer-reviewed research regarding type 1 diabetes. Researchers can receive up to $75K in funding for their projects allowing them to move forward with their work. Learn more about current projects and how to help by visiting http://diabetesresearchconnection.org.

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