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 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 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.
