It is known that patients with centrosomeand cilia defects have an elevated risk of developing diabetes, yet themolecular mechanisms underlying this association are not understood. Thecentrosome protein DISC1 (Disrupted in Schizophrenia 1) is a centrosome proteinthat also localizes to primary cilia and it is mutated in schizophrenicpatients who also have elevated predisposition to diabetes. The importance of DISC1in brain development and function is well recognized; however, nothing is knownabout its role in pancreatic beta cells, where it is also highly expressed.Since DISC1 is a direct interacting protein of pericentrin, and we have alreadyshown the importance of pericentrin for insulin secretion, I hypothesized thatdefects in DISC1 function or regulation in pancreatic beta cells may contributeto the development of diabetes. We anticipate that our studies will reveal thenormal function of DISC1 in pancreatic beta cells as well as provide insightsinto the high concordance of diabetes in schizophrenic patients.
Bardet-Biedl Syndrome (BBS) is a pleiotropicciliopathy characterized by a unique phenotype including obesity, type II diabetesand neurological impairments. The specific link between BBS and the developmentof type II diabetes among BBS patients is not currently understood. My researchexamines how loss of the Bardet-Biedl Syndrome 2 gene affects the function of pancreaticislets. The role of ciliary proteins in pancreatic islets will provide newinsights into the pathogenesis of diabetes and reveal potential new therapy fortreatments.