Role of SIRT1 Mutation in Onset of Type 1 Diabetes

Type 1 diabetes, caused by autoimmune-mediated β cell destruction, leads to insulin deficiency.  The histone deacetylase SIRT1 is prominently expressed in β cells and regulates insulin secretion².  SIRT1 plays a critical role in modulating several age-related diseases.  An article published in the journal Cell Metabolism describes a family carrying a mutation in the SIRT1 gene.  All five affected members developed an autoimmune disorder: four developed type 1 diabetes, and one developed ulcerative colitis.  Direct and exome sequencing identified the presence of a T-to-C exchange in exon 1 of SIRT1, corresponding to a leucine-to-proline mutation at residue 107. Expression of SIRT1-L107P in insulin-producing cells resulted in overproduction of nitric oxide, cytokines, and chemokines.  These observations identify a role for SIRT1 in human autoimmunity and unveil a monogenic form of type 1 diabetes.

Reference:

1.                  Biason-Lauber, et.al.  “Identification of a SIRT1 Mutation in a Family With Type 1 Diabetes.”  Cell Metabolism 17.  Supplement 3 (2013): 448 - 455.

2.                  Bordone, et al.  “SIRT1 Regulates Insulin Secretion by Expressing UCP2 in Pancreatic Beta Cells.”  PLoS Biology 4.  Supplement 2 (2006): e31.