JAX Atlas Links 58 Genes to Type 2 Diabetes Beta Cells

The Jackson Laboratory (JAX) has published a genomic atlas of human pancreatic islet cells that identifies dozens of previously overlooked genes linked to type 2 diabetes, with findings appearing in The EMBO Journal. The study, led by JAX Professor Michael L. Stitzel and staff scientist Khushdeep Bandesh, analyzed nearly 250,000 islet cells from 48 donors across non-diabetic, prediabetic, and diabetic states, resolving 14 distinct cell types in the process. Starting from 511 differentially active genes in beta cells from T2D patients, the team cross-referenced genomic, protein, and metabolic data in mouse models to narrow the field to 58 candidate genes likely playing causal roles. Two stand out: GRAMD2B, involved in insulin release, was consistently lower in T2D patients, and deleting it in mice produced glucose management defects. PDZK1 deletion did not disrupt mouse glucose regulation, but reducing it in human islets raised cell death rates. Neither gene had previously been associated with T2D. The study also confirmed a roughly 25% loss of beta cells in T2D and found the disease process is more beta-cell-specific than previously assumed. A separate finding implicates vitamin A metabolism: beta cells in T2D systematically reduce activity of genes that convert dietary vitamin A into retinoic acid, a molecule that supports cell survival under stress. The researchers note that whether vitamin A supplementation could be therapeutic requires dedicated clinical trials. The full dataset is publicly available, and multiple international research groups are already building on it, extending the atlas toward mapping inter-cell communication within islets.