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

Essam Refai, Nancy Dekki, Shao Nian Yang, Gabriela Imreh, Over Cabrera, Lina Yu, Guang Yang, Svante Norgren, Sophia M. Rössner, Luca Inverardi, Camillo Ricordi, Gunilla Olivecrona, Mats Andersson, Hans Jörnvall, Per Olof Berggren, Lisa Juntti-Berggren

Research output: Contribution to journalArticle

64 Scopus citations

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 languageEnglish (US)
Pages (from-to)17020-17025
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number47
DOIs
StatePublished - Nov 22 2005

Keywords

  • β-cell signal transduction
  • Apoptosis
  • Ca channels
  • Insulin release
  • Type 1 diabetes

ASJC Scopus subject areas

  • Genetics
  • General

Fingerprint Dive into the research topics of 'Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling'. Together they form a unique fingerprint.

  • Cite this

    Refai, E., Dekki, N., Yang, S. N., Imreh, G., Cabrera, O., Yu, L., Yang, G., Norgren, S., Rössner, S. M., Inverardi, L., Ricordi, C., Olivecrona, G., Andersson, M., Jörnvall, H., Berggren, P. O., & Juntti-Berggren, L. (2005). Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling. Proceedings of the National Academy of Sciences of the United States of America, 102(47), 17020-17025. https://doi.org/10.1073/pnas.0503219102