Loss of circulating insulin resulting from autoimmune destruction of β cells is the defining characteristic of type 1 diabetes (T1D), but islet dysfunction in T1D affects both β cells and α cells. Advances in multiomic analyses and the systematic collection of diseased human pancreata are enabling new approaches for diabetes research; hypotheses can be generated from observations in the affected human tissue and then tested in human islets, stem cell–derived islets, or humanized mice. The study by dos Santos and colleagues that appears in this issue of the JCI is an excellent example of the advantages and challenges posed by this approach. Through integrated analyses that combined electrophysiological and transcriptomic profiling, the authors provided detailed insights into the mechanisms leading to α cell dysfunction in islets from individuals with T1D.
Decio L. Eizirik, Priscila L. Zimath