Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling

E Refai, N Dekki, SN Yang, G Imreh… - Proceedings of the …, 2005 - National Acad Sciences
E Refai, N Dekki, SN Yang, G Imreh, O Cabrera, L Yu, G Yang, S Norgren, SM Rössner…
Proceedings of the National Academy of Sciences, 2005National Acad Sciences
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 …
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.
National Acad Sciences