December 2019 - Diabetes Research Connection

Diabetes Research News
December 30, 2019

Controlling Beta Cell Proliferation and Apoptosis to Manage Type 1 Diabetes

A key indicator of type 1 diabetes is lack of insulin-producing beta cells in the pancreas. These cells are mistakenly attacked and destroyed by the immune system leaving individuals unable to naturally manage their blood sugar. With little to no production of insulin, the body cannot effectively process sugars and use them as fuel. Instead, individuals must constantly monitor their blood glucose levels and administer insulin as needed.

However, a recent study uncovered how an FDA-approved drug for treating breast cancer may also be effective in diabetes care. Neratinib is a dual inhibitor of HER2 and EGFR kinases, but researchers have also found that it is incredibly effective at blocking mammalian sterile 20-like kinase 1 (MST1) as well. MST1 plays a key role in regulating beta cell proliferation and apoptosis. By inhibiting MST1 expression, insulin-producing beta cells may be protected from this process leading to greater beta cell survival and improved function.

In addition, when mouse models and human islets were treated with neratinib, they showed a marked improvement in glucose control and maintained lower overall glucose levels. The drug also restored expression of specific transcription factors such as PDX1 that contribute to glucose metabolism and insulin production.

Neratinib is an FDA-approved cancer treatment drug currently being used for breast cancer, but its effectiveness in treating other forms of cancer is being explored as well. Now researchers are examining whether its indications could be expanded to include diabetes. While it has been proven safe in cancer treatment, scientists are looking at ways to decrease its toxicity and improve specificity for diabetes.

In its current form, neratinib does not only target MST1 – it inhibits other kinases as well. Furthermore, there is concern that an extreme decrease in beta cell apoptosis could lead to increased expression of other cell types which could impact health. However, researchers can use this study as a foundation for exploring ways in which to refine the drug and improve beta-cell protection and function while minimizing other effects.

Diabetes Research Connection (DRC) is interested to see how this study impacts future treatment and prevention efforts in regard to type 1 diabetes. The DRC provides critical funding to early career scientists pursuing novel, peer-reviewed research projects focused on prevention, treatment, and improvement of quality of life for individuals living with the disease. This support can lead to scientific breakthroughs and have a significant impact on understanding of type 1 diabetes. Click to learn more about current projects and provide support.

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Diabetes Research News
December 23, 2019

Leveraging the Power of Light to Manage Type 1 Diabetes

A common problem in managing type 1 diabetes is maintaining relatively stable blood glucose levels. By the time a person realizes their blood sugar is rising or falling and begins to treat it, they may already experience spikes. This can be tough on the body and lead to over- or undertreatment in an effort to curb the highs or lows. Though technology has made it faster and easier to track blood glucose levels and more accurately administer insulin, it’s still not a perfect system.

A recent study reveals that researchers may have come up with a way to manage blood sugar without manually administering insulin. They engineered pancreatic beta cells to be responsive to exposure to blue light. By introducing a photoactivatable adenylate cyclase (PAC) enzyme into the cells, they produce a molecule that increases insulin production in response to high levels of glucose in the blood.

The molecule is turned on or off by blue light and can generate two to three times the typical amount of insulin produced by cells. However, it does not boost production when glucose levels in the blood are low. Furthermore, the cells do not require more oxygen than normal cells, which helps alleviate the common issue of oxygen starvation in transplanted cells.

The study was conducted on diabetic mice, so more research is needed to determine whether the process will be as effective in humans. If it is, this could mean that individuals with type 1 diabetes may have an option for controlling blood sugar levels without pharmacological intervention. When paired with a continuous glucose monitor (CGM) or other device as well as a source of blue light, it could create a closed loop model of managing the disease by functioning as a bioartificial pancreas.

This could be potentially life changing for individuals living with type 1 diabetes, and Diabetes Research Connection (DRC) is excited to see how the study progresses. Though not involved with this project, the DRC supports advancement of type 1 diabetes research and treatment options by providing critical funding for early career scientists pursuing novel research projects. Click to learn more about current projects and provide support.

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Diabetes Research News
December 16, 2019

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. Click to learn more about current projects and provide support.

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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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Diabetes Research News
December 2, 2019

Exploring the Use of Targeted Proteins in Managing Type 1 Diabetes

Currently, the most effective treatment for type 1 diabetes is the administration of insulin, but this is not a perfect solution. Since the body is unable to produce enough – or in some cases any – insulin on its own, individuals are tasked with carefully determining when and how much they need to keep blood sugar levels in check. This in itself can be challenging, and too much or too little insulin can lead to potentially life-threatening hyper- or hypoglycemia.

In addition to controlling blood sugar, insulin also helps regulate ketones within the blood. Ketones are created when lipids are broken down by the liver because the body is lacking glucose. Increased ketone levels can lead to diabetic ketoacidosis. Trouble controlling fat in the blood can put individuals at a greater risk for cardiovascular problems.

However, a recent study by researchers at the University of Geneva in Switzerland reveals that combining insulin with high doses of the protein S100A9 may improve regulation of glucose as well as lipids. Though it has only been tested in insulin-deficient diabetic mice thus far, the researchers are in the process of gaining approval for phase I human clinical trials. Other studies have already shown that there is a reduced risk of diabetes in individuals with higher levels of S100A9, so they are hopeful that this protein can play an integral role in diabetes management as well.

Another interesting discovery that the researchers made was that S100A9 was only effective when cells with TLR4 receptors were present as well. At this point, they are unsure exactly what the relationship is and why TLR4 is necessary for the process to work. However, their study leads the way toward reducing the amount of insulin necessary to effectively control blood glucose and ketone levels by combining it with the S100A9 protein.

Though not involved in this study, Diabetes Research Connection (DRC) is excited to see how it progresses once human clinical trials begin as it has the potential to impact treatment for millions of people living with type 1 diabetes. The DRC supports the advancement of research and treatment through providing critical funding to early career scientists pursuing novel research studies for the disease. Find out how to support these efforts and learn more about current projects by visiting https://diabetesresearchconnection.org.

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