Promising progress for new treatment of type 1 diabetes

 

Credit: Kailash Singh A representative image of islets from diabetic mice, which did not receive IL-35 (left) and received IL-35 (right). The brown color represent insulin producing beta cells. New research from Uppsala University shows promising progress in the use of anti-inflammatory cytokine for treatment of type 1 diabetes. The study, published in the open access journal Scientific Reports (Nature Publishing Group), reveals that administration of interleukin-35 (a protein made by immune cells) to mice with type 1 diabetes, reverses or cures the disease by maintaining a normal blood glucose level and the immune tolerance. Type 1 diabetes (T1D) is a chronic disease, which for the patients leads to a life-long dependence of daily injections of insulin. In Sweden approximately 2 new cases of the disease are diagnosed every day. Insulin is a hormone, which is produced by the beta cells in the pancreas. Insulin is required to prevent a harmful rise in the blood glucose level. The exact cause of T1D is not yet known, however, it is considered as an autoimmune disease. A condition that occurs when our own immune system by mistake attack and destroy healthy cells. In T1D, an infection and/or unknown factors probably triggers the immune cell attack, which ultimately leads to an insufficient insulin production. In the new study, Dr. Kailash Singh, a PhD student in professor Stellan Sandler's research group at the Department of Medical Cell Biology at Uppsala University, studied so-called immune regulatory T cells' actions in T1D mouse models. The study shows that the immune regulatory T cells alter their function by producing pro-inflammatory destructive proteins instead of protective anti-inflammatory proteins such as interleukin-35 (IL-35) under T1D conditions. "This suggests that the good guys have gone bad in early development of Type 1 diabetes and therefore our immune cells destroy the beta cell," says Dr. Kailash Singh. Furthermore, the concentration of IL-35 was lower in T1D patients compared to healthy individuals. These findings may suggest that IL-35 could play a crucial role in human T1D. In addition, the researchers have found a novel mechanism that explains how the immune regulatory T cells are changing their destiny under a T1D condition. Professor Sandler's research team tested whether or not IL-35 could also suppress development of T1D and reverse established T1D. To induce T1D in mice they injected a chemical compound called streptozotocin. These mice developed signs of TID and increasing blood glucose levels similar as in human T1D. IL-35 injections given after disease induction prevented from development of T1D. Strikingly, IL-35 injections to mice, which were diabetic for two consecutive days, normalized blood glucose concentrations. The research team also successfully investigated IL-35 in another model of T1D called non-obese diabetic mouse (NOD). The interruption of IL-35 treatment did not result in return of diabetes in any of the mouse models. The findings encourage further research on the use of IL-35 for treatment of T1D and offer new clues as to why immune regulatory T cells fail in counteracting T1D. "To the best of our knowledge, we are the first to show that IL-35 can reverse established Type 1 diabetes in two different mouse models and that the concentration of the particular cytokine is lower in Type 1 diabetes patients than in healthy individuals. Also, we are providing an insight into a novel mechanism: how immune regulatory T cells change their fate under autoimmune conditions," says Dr. Kailash Singh. Story Source: The above post is reprinted from materials provided by Uppsala Universitet. Note: Materials may be edited for content and length. Journal Reference: Kailash Singh, Erik Kadesjö, Julia Lindroos, Marcus Hjort, Marcus Lundberg, Daniel Espes, Per-Ola Carlsson, Stellan Sandler, Lina Thorvaldson. Interleukin-35 administration counteracts established murine type 1 diabetes – possible involvement of regulatory T cells. Scientific Reports, 2015; 5: 12633 DOI: 10.1038/srep12633 :

Tiny particles mimic the body's pancreas cells to combat type 1 diabetes

 

The researchers now plan to test the nanoparticle approach in human cells in vitro (Credit: Shutterstock) The destruction of the pancreatic cells that leads to type 1 diabetes arises when the body's own immune cells identify them as foreign targets and begin to attack them. But a new technique using tiny particles to mimic the form and function of the pancreatic cells is showing promise in halting the onset of the condition. The work undertaken by scientists from the Germans Trias i Pujol Research Institute and Catalan Institute for Nanoscience and Nanotechnology in Spain explores the potential for a type 1 diabetes vaccine. To start out with, the team developed an immunotherapy technique where the body's immune cells are extracted, modified and then re-injected. This is similar to a method used in promising rheumatoid arthritis research we covered last week, but it has major drawbacks in that it is both expensive and complicated. The researchers say they have now come up with a more practical method that yields the same results in mice. It concerns liposomes that feature an external fat membrane much like a regular cell. These measure 0.5 to one micron in diameter. The liposomes are made in the laboratory and designed to replicate the dying beta cells in the pancreas, which characterize type 1 diabetes. By introducing them to the body, the researchers found that they were effective in stopping the immune cells from destroying the beta cells and rendered the body able to tolerate their presence. Buoyed by the success in testing the technique in mice, the researchers now plan to run tests in human cells in vitro. From there, they hope to continue on to human trials and eventually work towards a cure for the disease by combining the approach with regenerative therapies. The research is to be published in the journal PLOS ONE. Source: Universitat Autònoma de Barcelona

Artificial pancreas shown to improve treatment of type 1 diabetes

 

 

The world’s first clinical trial comparing three alternative treatments for type 1 diabetes was conducted in Montréal by researchers at the IRCM and the University of Montreal, led by endocrinologist Dr. Rémi Rabasa-Lhoret. The study confirms that the external artificial pancreas improves glucose control and reduces the risk of hypoglycemia compared to conventional diabetes treatment. The world's first clinical trial comparing three alternative treatments for type 1 diabetes was conducted in Montréal by researchers at the IRCM and the University of Montreal, led by endocrinologist Dr. Rémi Rabasa-Lhoret. The study confirms that the external artificial pancreas improves glucose control and reduces the risk of hypoglycemia compared to conventional diabetes treatment. The results, published in the scientific journal The Lancet Diabetes & Endocrinology, could have a significant impact on the treatment of type 1 diabetes, a chronic disease that can cause vision loss and cardiovascular diseases. An emerging technology to treat type 1 diabetes, the external artificial pancreas is an automated system that simulates the normal pancreas by continuously adapting insulin delivery based on changes in glucose levels. Two configurations exist: the single-hormone artificial pancreas that delivers insulin alone and the dual-hormone artificial pancreas that delivers both insulin and glucagon. While insulin lowers blood glucose levels, glucagon has the opposite effect and raises glucose levels. "Our clinical trial was the first to compare these two configurations of the artificial pancreas with the conventional diabetes treatment using an insulin pump," says Dr. Rabasa-Lhoret, Director of the Obesity, Metabolism and Diabetes research clinic at the IRCM and professor at the University of Montreal's Department of Nutrition. "We wanted to determine the usefulness of glucagon in the artificial pancreas, especially to prevent hypoglycemia, which remains the major barrier to reaching glycemic targets." People living with type 1 diabetes must carefully manage their blood glucose levels to ensure they remain within a target range in order to prevent serious long-term complications related to high glucose levels (such as blindness or kidney failure) and reduce the risk of hypoglycemia (dangerously low blood glucose that can lead to confusion, disorientation and, if severe, loss of consciousness, coma and seizure). "Our study confirms that both artificial pancreas systems improve glucose control and reduce the risk of hypoglycemia compared to conventional pump therapy," explains engineer Ahmad Haidar, first author of the study and postdoctoral fellow in Dr. Rabasa-Lhoret's research unit at the IRCM. "In addition, we found that the dual-hormone artificial pancreas provides additional reduction in hypoglycemia compared to the single-hormone system." "Given that low blood glucose remains very frequent during the night, the fear of severe nocturnal hypoglycemia is a major source or stress and anxiety, especially for parents with young diabetic children," adds Dr. Laurent Legault, paediatric endocrinologist at the Montreal Children's Hospital, and co-author of the study. "The artificial pancreas has the potential to substantially improve the management of diabetes and the quality of life for patients and their families." IRCM researchers are pursuing clinical trials on the artificial pancreas to test the system for longer periods and with larger patient cohorts. The technology should be available commercially within the next five to seven years, with early generations focusing on overnight glucose control. According to the Canadian Diabetes Association, an estimated 285 million people worldwide are affected by diabetes, approximately 10 per cent of which have type 1 diabetes. With a further 7 million people developing diabetes each year, this number is expected to hit 438 million by 2030, making it a global epidemic. Today, more than nine million Canadians -- or one if four -- are living with diabetes or prediabetes. Story Source: The above story is based on materials provided by Universite de Montreal. Note: Materials may be edited for content and length. Journal Reference: Ahmad Haidar, Laurent Legault, Virginie Messier, Tina Maria Mitre, Catherine Leroux, Rémi Rabasa-Lhoret. Comparison of dual-hormone artificial pancreas, single-hormone artificial pancreas, and conventional insulin pump therapy for glycaemic control in patients with type 1 diabetes: an open-label randomised controlled crossover trial. The Lancet Diabetes & Endocrinology, 2014; DOI: 10.1016/S2213-8587(14)70226-8