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Gene with Role in Type 2 Diabetes Found to Also Drive a Range of Psychiatric Ills

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Gene with Role in Type 2 Diabetes Found to Also Drive a Range of Psychiatric Ills
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Type 2 diabetes is known to be more common in people with psychiatric disorders, such as depressionbipolar disorder and schizophrenia. Now, researchers at the Diabetes Center of Excellence at the University of Massachusetts Medical School found that the gene DISC1 — believed to play a role in these psychiatric illnesses — also contributes to type 2 diabetes.

DISC-1 is short for disrupted in schizophrenia 1, and the gene is among the most convincing genetic risk factors for this disorder. Following its discovery in schizophrenia, scientists also learned that it played a role in bipolar disorder and some forms of depression. Based on the high rates of comorbidity between diabetes and psychiatric disorders, the research team, led by Rita Bortell, wanted to explore if DISC1 could also affect diabetes pathology.

The team studied mice manipulated to have the DISC1 gene disrupted in the insulin-producing pancreatic cells and normal mice. Comparisons of the two showed that the mice lacking DISC1 had an increased death rate of pancreatic insulin-producing beta cells. Consequently, these animals produced less insulin and showed signs of an impaired glucose regulation.

“Studies exploring the biology of disease have increasingly identified the involvement of unanticipated proteins — DISC1 fits this category,” Dr. Bortell said in a press release. “Our hope is that the association we’ve found linking disrupted DISC1 to both diabetes and psychiatric disorders may uncover mechanisms to improve therapies, even preventative ones, to alleviate suffering caused by both illnesses which are extraordinarily costly, very common, often quite debilitating.”

According to the study results, published in The FASEB Journal under the title “Beyond the brain: disrupted in schizophrenia 1 regulates pancreatic β-cell function via glycogen synthase kinase-3β,” the team found that DISC1 regulates the activity of the protein GSK3β, which has a confirmed role in the function and survival of beta cells. Lack of DISC1 increased activation of GSK3β in beta cells, and when researchers inhibited GSK3β in mice lacking DISC1, they noticed improved beta cell survival. The glucose tolerance of the DISC1-lacking mice was also restored upon blockage of GSK3β.

According to the release, FASEB editor in chief, Thoru Pederson, said of the findings, “The connections between these disorders may be surprising, but we have known for a long time that a single protein or gene can play multiple roles in the body.”

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