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Genetic cause found for loss of beta cells during diabetes development

Understanding a hidden killer

Date:
March 24, 2016
Source:
University of Montreal
Summary:
A common genetic defect in beta cells may underlie both known forms of diabetes, new research has found. Thanks to our genetic make-up, some of us have beta cells that are tough and robust, while others have beta cells that are fragile and can't handle stress. It is these people who develop diabetes, either type 1 or type 2.
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New research by Dr. Sylvie Lesage, scientist at Maisonneuve-Rosemont Hospital (CIUSSS- East Montreal) and associate research Professor at University of Montreal, just published in the international scientific journal Nature Genetics, has discovered that a common genetic defect in beta cells may underlie both known forms of diabetes.

Worldwide, 400 million people suffer from diabetes, with rapid increases projected. Patients with diabetes mostly fall into one of two categories, type 1 diabetics, triggered by autoimmunity at a young age, and type 2 diabetics, caused by metabolic dysfunction of the liver. Despite being labeled a "lifestyle disease," diabetes has a strong genetic basis.

"Our research finds that genetics is critical for the survival of beta cells -- the cells that make insulin'' says Sylvie Lesage, who is also a member of the Montreal Diabetes Research Center. ''Thanks to our genetic make-up, some of us have beta cells that are tough and robust, while others have beta cells that are fragile and can't handle stress. It is these people who develop diabetes, either type 1 or type 2, while others with tougher beta cells will remain healthy even in if they suffer from autoimmunity or metabolic dysfunction of the liver."

Different pathways to diabetes development

Diabetes is a hidden killer. One out of every 11 adults is suffering from the disease, yet half of them have not even been diagnosed. Diabetes is caused by the inability of the body to lower blood glucose, a process normally driven by insulin. In patients with type 1 diabetes (T1D), this is caused by the immune system killing off the beta cells that produce insulin. In patients with type 2 diabetes (T2D), a metabolic dysfunction prevents insulin from working on the liver. In both cases, left untreated the extra glucose in the blood can cause blindness, cardiovascular disease, diabetic nephropathy, diabetic neuropathy and death.

In this study led by Dr. Adrian Liston, an international team of researchers investigated how genetic variation controls the development of diabetes. While most previous work has focused on the effect of genetics in altering the immune system (in T1D) and metabolic dysfunction of the liver (in T2D), this research found that genetics also affected the beta cells that produce insulin. Mice with fragile beta cells that were poor at repairing DNA damage would rapidly develop diabetes when those beta cells were challenged by cellular stress. Other mice, with robust beta cells that were good at repairing DNA damage, were able to stay non-diabetic for life, even when those islets were placed under severe cellular stress. The same pathways for beta cell survival and DNA damage repair were also found to be altered in diabetic patient samples, indicating that a genetic predisposition for fragile beta cells may underlie who develops diabetes.

A new model for testing type 2 diabetes treatments

Current treatments for T2D rely on improving the metabolic response of the liver to insulin. These antidiabetic drugs, in conjunction with lifestyle interventions, can control the early stages of T2D by allowing insulin to function on the liver again. However during the late stages of T2D, the death of beta cells means that there is no longer any insulin being produced. At this stage, antidiabetic drugs and lifestyle interventions have poor efficacy, and medical complications arise.

Dr. Lydia Makaroff, of the International Diabetes Federation, commented this ground breaking work: ''The health cost for diabetes currently exceeds US$600 billion worldwide, 12 % of the global health budget, and will only increase as diabetes becomes more common. Much of this health care burden is caused by late-stage type 2 diabetes, where we do not have effective treatments, so we desperately need new research into novel therapeutic approaches. This discovery dramatically improves our understanding of type 2 diabetes, which will enable the design of better strategies and medications for diabetes in the future."

Dr. Adrian Liston, leader of the Belgian arm of the research, sees new promise in these results, especially through the new animal models used which will enable scientists, for the first time, to test new antidiabetic drugs that focus on preserving beta cells.


Story Source:

Materials provided by University of Montreal. Note: Content may be edited for style and length.


Journal Reference:

  1. James Dooley, Lei Tian, Susann Schonefeldt, Viviane Delghingaro-Augusto, Josselyn E Garcia-Perez, Emanuela Pasciuto, Daniele Di Marino, Edward J Carr, Nikolay Oskolkov, Valeriya Lyssenko, Dean Franckaert, Vasiliki Lagou, Lut Overbergh, Jonathan Vandenbussche, Joke Allemeersch, Genevieve Chabot-Roy, Jane E Dahlstrom, D Ross Laybutt, Nikolai Petrovsky, Luis Socha, Kris Gevaert, Anton M Jetten, Diether Lambrechts, Michelle A Linterman, Chris C Goodnow, Christopher J Nolan, Sylvie Lesage, Susan M Schlenner, Adrian Liston. Genetic predisposition for beta cell fragility underlies type 1 and type 2 diabetes. Nature Genetics, 2016; DOI: 10.1038/ng.3531

Cite This Page:

University of Montreal. "Genetic cause found for loss of beta cells during diabetes development: Understanding a hidden killer." ScienceDaily. ScienceDaily, 24 March 2016. <www.sciencedaily.com/releases/2016/03/160324082835.htm>.
University of Montreal. (2016, March 24). Genetic cause found for loss of beta cells during diabetes development: Understanding a hidden killer. ScienceDaily. Retrieved May 23, 2017 from www.sciencedaily.com/releases/2016/03/160324082835.htm
University of Montreal. "Genetic cause found for loss of beta cells during diabetes development: Understanding a hidden killer." ScienceDaily. www.sciencedaily.com/releases/2016/03/160324082835.htm (accessed May 23, 2017).

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