Matthew Wortham, Bastian Ramms, Chun Zeng, Jacqueline R Benthuysen, Somesh Sai, Dennis P Pollow, Fenfen Liu, Michael Schlichting, Austin R Harrington, Bradley Liu, Thazha P Prakash, Elaine C Pirie, Han Zhu, Siyouneh Baghdasarian, Johan Auwerx, Orian S Shirihai, Maike Sander
Selective and controlled expansion of endogenous β-cells has been pursued as a potential therapy for diabetes. Ideally, such therapies would preserve feedback control of β-cell proliferation to avoid excessive β-cell expansion and an increased risk of hypoglycemia. Here, we identified a regulator of β-cell proliferation whose inactivation results in controlled β-cell expansion: the protein deacetylase Sirtuin 2 (SIRT2). Sirt2 deletion in β-cells of mice increased β-cell proliferation during hyperglycemia with little effect in homeostatic conditions, indicating preservation of feedback control of β-cell mass...
February 28, 2024: bioRxiv