title: Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling.
abstract: Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic beta-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca(2+) channels. TTR also protected against beta-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal beta-cell function. Conversion of TTR tetramer to monomer may be involved in the development of beta-cell failure/destruction in type 1 diabetes.
authors.affiliation: Department of Medical Biochemistry and Biophysics, The Rolf Luft Center for Diabetes Research, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Essam
authors.initials: E
authors.lastname: Refai
authors.forename: Nancy
authors.initials: N
authors.lastname: Dekki
authors.forename: Shao-Nian
authors.initials: SN
authors.lastname: Yang
authors.forename: Gabriela
authors.initials: G
authors.lastname: Imreh
authors.forename: Over
authors.initials: O
authors.lastname: Cabrera
authors.forename: Lina
authors.initials: L
authors.lastname: Yu
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Svante
authors.initials: S
authors.lastname: Norgren
authors.forename: Sophia M
authors.initials: SM
authors.lastname: Rössner
authors.forename: Luca
authors.initials: L
authors.lastname: Inverardi
authors.forename: Camillo
authors.initials: C
authors.lastname: Ricordi
authors.forename: Gunilla
authors.initials: G
authors.lastname: Olivecrona
authors.forename: Mats
authors.initials: M
authors.lastname: Andersson
authors.forename: Hans
authors.initials: H
authors.lastname: Jörnvall
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Berggren
authors.forename: Lisa
authors.initials: L
authors.lastname: Juntti-Berggren
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D005947:Glucose / Q000502:physiology; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008820:Mice, Obese; D018408:Patch-Clamp Techniques; D011189:Potassium Chloride; D011228:Prealbumin / Q000502:physiology*
chemical_list: D011228:Prealbumin; D011189:Potassium Chloride; D005947:Glucose; D002118:Calcium