Diabetes is characterized by high blood glucose levels caused by the inability of pancreatic β-cells to produce sufficient insulin to meet the body’s needs. Diabetes is driven by both genetic and environmental factors. Excess body iron is one known risk factor in the development of diabetes. Iron deficiency is associated with obesity, a known diabetes risk factor. Research in the lab of Elizabeth Leibold, PhD, showed that in mice with iron deficiency, proinsulin processing to mature insulin was impaired, resulting in reduced levels of circulating and glucose intolerance. Mice treated with iron restored insulin to normal levels and eliminated the glucose intolerance. Further biochemical studies showed the precise molecular mechanism by which iron deficiency impairs insulin production in β-cells. These studies reveal a previously unidentified link between insulin processing and cellular iron deficiency that enhances our understanding of pathobiology of iron deficiency and diabetes, and may have therapeutic implications.
Irp2 regulates insulin production through iron-mediated Cdkal1-catalyzed tRNA modification. dos Santos MCF, Anderson CP, Neschen S, Zumbrennen-Bullough KB, Romney SJ, Kahle-Stephan M, Rathkolb B, Gailus-Durner V, Fuchs H, Wolf E, Rozman J, de Angelis MH, Cai WM, Rajan M, Hu J, Dedon PC, Leibold EA. Nat Commun. 2020 Jan;11(1):296.