title: Diabetes in Friedreich ataxia.
abstract: Diabetes is a common metabolic disorder in patients with Friedreich ataxia. In this Supplement article, we review the clinical data on diabetes in Friedreich ataxia, and the experimental data from rodent and in vitro models of the disease. Increased body adiposity and insulin resistance are frequently present in Friedreich ataxia, but pancreatic β cell dysfunction and death are a conditio sine qua non for the loss of glucose tolerance and development of diabetes. The loss of frataxin function in mitochondria accounts for these pathogenic processes in Friedreich ataxia. Mitochondria are essential for the sensing of nutrients by the β cell and for the generation of signals that trigger and amplify insulin secretion, known as stimulus-secretion coupling. Moreover, in the intrinsic pathway of apoptosis, pro-apoptotic signals converge on mitochondria, resulting in mitochondrial Bax translocation, membrane permeabilization, cytochrome c release and caspase cleavage. How and at which level frataxin deficiency impacts on these processes in β cells is only partially understood. A better understanding of the molecular mechanisms mediating β cell demise in Friedreich ataxia will pave the way for new therapeutic approaches.
authors.affiliation: Laboratory of Experimental Medicine, Université Libre de Bruxelles, Brussels, Belgium. mcnop@ulb.ac.be
authors.forename: Miriam
authors.initials: M
authors.lastname: Cnop
authors.forename: Hindrik
authors.initials: H
authors.lastname: Mulder
authors.forename: Mariana
authors.initials: M
authors.lastname: Igoillo-Esteve
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000502:physiology; D003920:Diabetes Mellitus / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005621:Friedreich Ataxia / Q000150:complications* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D033862:Iron-Binding Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000150:complications; D010179:Pancreas / Q000473:pathology; D012306:Risk; D000096923:Frataxin
chemical_list: D007328:Insulin; D033862:Iron-Binding Proteins; D000096923:Frataxin
keywords: Friedreich ataxia; apoptosis; diabetes; insulin; insulin resistance; pancreatic beta cell