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

doi:10.1073/pnas.0503219102

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 journal › Article

62 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 language	English (US)
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	https://doi.org/10.1073/pnas.0503219102
State	Published - Nov 22 2005

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Keywords

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

ASJC Scopus subject areas

Genetics
General

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

Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling. / Refai, Essam; Dekki, Nancy; Yang, Shao Nian; Imreh, Gabriela; Cabrera, Over; Yu, Lina; Yang, Guang; Norgren, Svante; Rössner, Sophia M.; Inverardi, Luca; Ricordi, Camillo; Olivecrona, Gunilla; Andersson, Mats; Jörnvall, Hans; Berggren, Per Olof; Juntti-Berggren, Lisa.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 47, 22.11.2005, p. 17020-17025.

Research output: Contribution to journal › Article

Refai, E, Dekki, N, Yang, SN, Imreh, G, Cabrera, O, Yu, L, Yang, G, Norgren, S, Rössner, SM, Inverardi, L, Ricordi, C, Olivecrona, G, Andersson, M, Jörnvall, H, Berggren, PO & 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, vol. 102, no. 47, pp. 17020-17025. https://doi.org/10.1073/pnas.0503219102

Refai, Essam ; Dekki, Nancy ; Yang, Shao Nian ; Imreh, Gabriela ; Cabrera, Over ; Yu, Lina ; Yang, Guang ; Norgren, Svante ; Rössner, Sophia M. ; Inverardi, Luca ; Ricordi, Camillo ; Olivecrona, Gunilla ; Andersson, Mats ; Jörnvall, Hans ; Berggren, Per Olof ; Juntti-Berggren, Lisa. / Transthyretin constitutes a functional component in pancreatic β-cell stimulus-secretion coupling. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 47. pp. 17020-17025.

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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.",

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AU - Yu, Lina

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AU - Norgren, Svante

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AU - Inverardi, Luca

AU - Ricordi, Camillo

AU - Olivecrona, Gunilla

AU - Andersson, Mats

AU - Jörnvall, Hans

AU - Berggren, Per Olof

AU - Juntti-Berggren, Lisa

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10.1073/pnas.0503219102