1. Transthyretin constitutes a functional component in pancreatic β-celI stimulus--secretion coupling.
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Refai, Essam, Dekki, Nancy, Shao-Nian Yang, Imreh, Gabriela, Cabrera, Over, Lina Yu, Guang Yang, Norgren, Svante, Rössner, Sophia M., Inverardi, Luca, Ricordi, Camillo, Olivecrona, Gunilla, Andersson, Mats, Jörnvall, Hans, Berggren, Per-Olof, and Juntti-Berggren, Lisa
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PANCREATIC beta cells ,BLOOD plasma ,BIOLOGICAL transport ,GLUCOSE ,CARRIER proteins ,HYPOGLYCEMIC agents - 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 ([Ca²+ ]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. [ABSTRACT FROM AUTHOR]- Published
- 2005
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