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Targeting the Effects of Specific Drugs on Pancreatic Islets

The production of insulin and glucagon used to regulate blood sugar levels come from pancreatic islet cells. In individuals with type 1 diabetes, the immune system mistakenly attacks and destroys these cells leaving the body unable to naturally regulate blood sugar. That means that individuals must continuously monitor and manage these levels themselves.

A recent study examined the impact that specific drugs have on pancreatic islet cells and their function. Researchers were able to fine-tune single-cell transcriptomics to remove contamination from RNA molecules that could interfere with results and negatively affect reliability of the data.

Once they had created decontaminated transcriptomes, they tested three different drugs that relate to blood glucose management. They found that one drug, FOXO1, “induces dedifferentiation of both alpha and beta cells,” while the drug artemether “had been found to diminish the function of alpha cells and could induce insulin production in both in vivo and in vitro studies.” They compared these drugs in both human and mouse samples to determine if there were any differences in how the cells responded. One notable difference was that artemether did not have a significant impact on insulin expression in human cells, but in mouse cells, there was reduced insulin expression and overall beta cell identity.

Single-cell analysis of various drugs could help guide future therapeutic treatments for type 1 diabetes as researchers better understand their impact. Targeted therapies have become a greater focus of research as scientists continue to explore T1D at a cellular level.

Diabetes Research Connection (DRC) is interested to see how single-cell sequencing and the ability to decontaminate RNA sequences could affect diabetes research. The organization supports a wide array of T1D-focused studies by providing critical funding to allow early-career scientists to advance their research. To learn more and support these efforts, visit https://diabetesresearchconnection.org.

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Improving Vascularization of Transplanted Islet Cells

One option that researchers have explored for treating type 1 diabetes is cell transplantation. By introducing new pancreatic islet cells, they aim to better control glucose levels and insulin production. However, there are still many challenges surrounding this approach including cell death due to poor vascularization.

Pancreatic islet cells are highly vascularized in order to quickly and easily transport insulin. If they are not able to establish blood vessel connections following transplantation, they cannot work as effectively and may not survive long-term. A recent study has found an improved method for promoting vascularization and enabling more effective cell transplantation.

A multidisciplinary team of researchers developed a biomimetic microvascular mesh that maintained its shape and promoted the survival of transplanted cells by stimulating revascularization. When transplanted into diabetic mouse models, they were able to maintain normoglycemia for up to three months.

The researchers created micropillars to improve anchoring of the microvascular mesh and decrease risk of shrinkage as cells matured. They had success using both human umbilical vein endothelial cells (HUVECs) and human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) in the meshes. Compared to a mesh without these cells, the mesh with the cells showed both anastomoses and vascular remodeling which are essential in vascularization during cell replacement therapy.

Though they have only been tested in mouse models, biomimetic microvascular mesh could one day be used to improve cell replacement therapy for humans with type 1 diabetes in order to improve glycemic control. This study opens doors for additional research and further refining islet transplantation methods.

Though not involved with this study, Diabetes Research Connection (DRC) supports novel research projects that strive to advance treatment for type 1 diabetes and one day find a cure. Early career scientists can receive up to $75K in funding from donations by individuals, corporations, and foundations to support their research. Learn more by visiting http://diabetesresearchconnection.org.

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Could Improving Cell-to-Cell Communication Enhance Cell Replacement Therapy Options for Type 1 Diabetes?

Researchers have been exploring the potential of stem cell therapies for years, however this is a very challenging endeavor because there are many factors that influence cell development, differentiation, and fate. In the case of type 1 diabetes, researchers have been studying methods for preventing the destruction of insulin-producing beta cells, stimulating the generation of new cells, and directing differentiation of stem cells among other strategies.

In a recent study, scientists focused on enhancing cell-to-cell communication in order to influence differentiation of embryonic stem cells. They examined the role of Connexin 43 (Cx43) specifically, which is a gap junction (GJ) channel protein. Scientists found that by using the AAP10 peptide to activate Cx43 GJ channels, they could steer differentiation of cells toward definitive endoderm and primitive gut tube lineages. In turn, with improved communication between cells triggered by the AAP10 peptide, definitive endoderm cells were more likely to become pancreatic progenitors and pancreatic endocrine progenitors.

Pancreatic progenitors (PP) and pancreatic endocrine progenitors (PE) play a role in the development of pancreatic islet cells which produce insulin and glucagon. These are the same cells that the body mistakenly attacks and destroys in individuals with type 1 diabetes. The ability to influence the differentiation of human embryonic stem cells into PPs and PEs may support improved cell replacement therapies for diabetes.

There is still a great deal of research to be done as it is difficult to manipulate the mechanisms of cell communication in order to produce desired results. Scientists are also continuing to investigate whether improved intercellular communication could lead to an increased production of pancreatic islet cells.

Researchers involved in this study include Dr. Wendy Yang, Dr. Laura Crisa, and Dr. Vincenzo Cirulli. Yang’s research is funded by Diabetes Research Connection (DRC) and Crisa and Cirulli are part of the DRC’s scientific review committee. To learn more about the DRC and the funding it provides to support type 1 diabetes research, visit http://diabetesresearchconnection.org.

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Could Peripheral T Helper Cells Be Linked to Type 1 Diabetes Risk?

Type 1 diabetes (T1D) is a complex disease. Researchers believe that both genetics and autoantibodies play a role in development of the disease. In individuals with T1D, the immune system mistakenly attacks and destroys insulin-producing beta cells in the pancreas. A new study has found that peripheral T helper cells may play a role in initiating this process.

The study showed that children with T1D, as well as those who were autoantibody-positive who developed the disease later on, both had an increase in the amount of peripheral T helper cells circulating in their blood. Researchers believe that much like follicular helper T cells, peripheral T helper cells may also be involved in activating B cells which target against proteins in pancreatic islet cells and contribute to the development of T1D.

The ability to identify children who are at increased risk for the disease due to genetics as well as the elevated presence of peripheral T helper cells may improve options for proactively monitoring and treating T1D. It could also support the development of new immunotherapies for the disease.

More research is necessary to better understand the role of this T-cell subset and how it impacts type 1 diabetes risk and development of the disease as well as how it could improve treatment or prevention options. Though not involved with this study, Diabetes Research Connection (DRC) follows the latest developments and advancements regarding type 1 diabetes understanding, treatment, and prevention.

DRC provides critical funding for early career scientists pursuing novel research studies related to the disease and hopes to one day find a cure. To learn more about current projects or how to help, visit http://diabetesresearchconnection.org.

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