Type 1 diabetes (T1D) is an autoimmune disease in which the body’s immune cells attack and destroy the beta cells of the pancreas that produce insulin.
Researchers have long tried to unravel the signaling that provokes this attack. One of the less-studied forms of signaling is inflammatory lipids.
In a study published in JCI Insight, Sasanka Ramanadham and colleagues at UAB, other universities in the U.S. and in Greece have identified a proinflammatory lipid profile (iPLA2) that precedes development of T1D in mice and in children younger than 15 who are at high risk for T1D. This finding may identify therapeutic targets to prevent T1D.
Ramanadham and others have shown that iPLA2 participates in the programmed death of beta cells and promotes T-cell immune responses.
“In light of these observations,” said Ramanadham, a professor in the UAB Department of Cell, Developmental and Integrative Biology and senior scientist in the UAB Comprehensive Diabetes Center, “we used lipidomics to gain insight into the lipidome associated with T1D development in spontaneous-T1D-prone non-obese diabetic mice, or NOD mice, and in humans at high risk for developing T1D.”
About 80% to 90% of NOD mice become diabetic by 25 to 30 weeks of age; if an iPLA2-beta inhibitor was given to the mice starting at 10 days, only 10% to 15% of the NOD mice developed diabetes. But if the inhibitor was started later, at four or eight weeks, the researchers saw that about 60% or 80%, respectively, of the mice developed diabetes.
Additionally, the researchers found pro-inflammatory lipid signatures similar to the mice in the blood plasma of children between 9 and 15 years of age, who were at high risk for developing T1D, as measured by autoantibodies.
“These findings,” Ramanadham said, “suggest that iPLA2-beta-derived lipids contribute to T1D onset, and they identify select lipids that could be targeted for therapeutics and – in conjunction with autoantibodies – serve as early biomarkers of pre-T1D.”
Co-first authors of the study, “Lipid mediators and biomarkers associated with Type 1 diabetes development,” are Alexander J. Nelson, UAB Department of Cell, Developmental and Integrative Biology and the UAB Comprehensive Diabetes Center; Daniel J. Stephenson, University of South Florida; and Robert N. Bone, Indiana University School of Medicine.
Other co-authors with Ramanadham are Christopher L. Cardona, Margaret A. Park and Charles E. Chalfant, University of South Florida; Ying G. Tusing and Xiaoyong Lei, UAB Department of Cell, Developmental and Integrative Biology and the UAB Comprehensive Diabetes Center; George Kokotos, National and Kapodistrian University of Athens, Greece; Christina L. Graves, University of North Carolina, Chapel Hill; Clayton E. Mathews, University of Florida Health Science Center; and Joanna Kramer and Martin J. Hessner, College of Wisconsin and Children’s Research Institute of Children’s Hospital of Wisconsin. Chalfant also serves at the James A. Haley Veterans Hospital in Tampa, Florida.
Support came from the UAB Department of Cell, Developmental and Integrative Biology; the Stavros Niarchos Foundation; a University of South Florida initiative; and grants from JDRF, the Veterans Administration and the National Institutes of Health.
This story originally appeared on the University of Alabama at Birmingham’s UAB News website.
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September 29, 2020 at 04:02AM
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