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 (US) |
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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 |
Keywords
- β-cell signal transduction
- Apoptosis
- Ca channels
- Insulin release
- Type 1 diabetes
ASJC Scopus subject areas
- Genetics
- General