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 β-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca2+ concentration ([Ca 2+]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca2+ channels. TTR also protected against β-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 β-cell function. Conversion of TTR tetramer to monomer may be involved in the development of β-cell failure/ destruction in type 1 diabetes.
| Original language | English |
|---|---|
| Pages (from-to) | 17020-17025 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 102 |
| Issue number | 47 |
| DOIs | |
| State | Published - Nov 22 2005 |
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Keywords
- β-cell signal transduction
- Apoptosis
- Ca channels
- Insulin release
- Type 1 diabetes
ASJC Scopus subject areas
- Genetics
- General
Cite this
Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling. / Refai, Essam; Dekki, Nancy; Yang, Shao Nian; Imreh, Gabriela; Cabrera, Over; Yu, Lina; Yang, Guang; Norgren, Svante; Rössner, Sophia M.; Inverardi, Luca A; Ricordi, Camillo; Olivecrona, Gunilla; Andersson, Mats; Jörnvall, Hans; Berggren, Per Olof; Juntti-Berggren, Lisa.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 47, 22.11.2005, p. 17020-17025.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling
AU - Refai, Essam
AU - Dekki, Nancy
AU - Yang, Shao Nian
AU - Imreh, Gabriela
AU - Cabrera, Over
AU - Yu, Lina
AU - Yang, Guang
AU - Norgren, Svante
AU - Rössner, Sophia M.
AU - Inverardi, Luca A
AU - Ricordi, Camillo
AU - Olivecrona, Gunilla
AU - Andersson, Mats
AU - Jörnvall, Hans
AU - Berggren, Per Olof
AU - Juntti-Berggren, Lisa
PY - 2005/11/22
Y1 - 2005/11/22
N2 - 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 β-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca2+ concentration ([Ca 2+]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca2+ channels. TTR also protected against β-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 β-cell function. Conversion of TTR tetramer to monomer may be involved in the development of β-cell failure/ destruction in type 1 diabetes.
AB - 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 β-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca2+ concentration ([Ca 2+]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltage-gated Ca2+ channels. TTR also protected against β-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 β-cell function. Conversion of TTR tetramer to monomer may be involved in the development of β-cell failure/ destruction in type 1 diabetes.
KW - β-cell signal transduction
KW - Apoptosis
KW - Ca channels
KW - Insulin release
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=28044470481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=28044470481&partnerID=8YFLogxK
U2 - 10.1073/pnas.0503219102
DO - 10.1073/pnas.0503219102
M3 - Article
C2 - 16286652
AN - SCOPUS:28044470481
VL - 102
SP - 17020
EP - 17025
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 47
ER -