title: Regular insulin secretory oscillations despite impaired ATP synthesis in Friedreich Ataxia patients.
abstract: Friedreich Ataxia is an inherited disorder caused by decreased expression of a mitochondrial protein called frataxin. Deficiency of this protein causes reduced biogenesis of iron-sulfur clusters, and subsequently impaired synthesis and replenishment of ATP IN VIVO. Basal secretion of insulin occurs in an oscillating manner presumably triggered by ATP-dependent feedback inhibition of glycolytic flux. Hence, individuals with reduced ATP synthesis rates should possibly exhibit impaired insulin secretory oscillations if these were solely dependent on ATP. In the present study Friedreich Ataxia patients with a presumptive impairment of ATP synthesis in pancreatic beta-cells were evaluated for regularity of basal secretory oscillations of insulin. Healthy siblings were employed as controls. In conflict with the initial hypothesis, no differences in regards to oscillation patterns were observed between patients and controls. Supported by EX VIVO evidence, these findings tentatively suggest that pulsatile insulin secretion might not be exclusively dependent on ATP feedback inhibition in humans.
authors.affiliation: Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Meyer
authors.forename: H
authors.initials: H
authors.lastname: Carlqvist
authors.forename: M
authors.initials: M
authors.lastname: Vorgerd
authors.forename: L
authors.initials: L
authors.lastname: Schöls
authors.forename: C-G
authors.initials: CG
authors.lastname: Ostenson
authors.forename: M
authors.initials: M
authors.lastname: Ristow
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005621:Friedreich Ataxia / Q000150:complications / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D010085:Oxidative Phosphorylation; D010507:Periodicity; D011673:Pulsatile Flow; D000096923:Frataxin
chemical_list: D000255:Adenosine Triphosphate; D007328:Insulin; D033862:Iron-Binding Proteins; D000096923:Frataxin