Transthyretin constitutes a functional component in pancreatic beta-cell stimulus-secretion coupling.
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.
Refai
Essam
E
Department of Medical Biochemistry and Biophysics, The Rolf Luft Center for Diabetes Research, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Dekki
Nancy
N
Yang
Shao-Nian
SN
Imreh
Gabriela
G
Cabrera
Over
O
Yu
Lina
L
Yang
Guang
G
Norgren
Svante
S
Rössner
Sophia M
SM
Inverardi
Luca
L
Ricordi
Camillo
C
Olivecrona
Gunilla
G
Andersson
Mats
M
Jörnvall
Hans
H
Berggren
Per-Olof
PO
Juntti-Berggren
Lisa
L
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*
D011228:Prealbumin; D011189:Potassium Chloride; D005947:Glucose; D002118:Calcium