Role of Insulin-Like Growth Factor-Binding Protein 5 (IGFBP5) in Organismal and Pancreatic β-Cell Growth

Catherine E. Gleason, Yun Ning, Tara P. Cominski, Rana K Gupta, Klaus H. Kaestner, John E. Pintar, Morris J. Birnbaum

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

A family of IGF-binding proteins (IGFBP) exerts biological actions both dependentonand independent of IGF-I. A major effector of the insulin/IGF-I signaling pathway, the serine/threonine protein kinase Akt, mediates cellular processes such as glucose uptake, protein synthesis, cell survival, and growth. IGF-I is required for normal organismal growth, and in the pancreatic β-cell, the insulin/IGF-I signaling pathway is critical for normal and adaptive maintenance of β-cell mass. Expression of myrAkt1, an activated form of Akt, in the endocrine pancreas drives β-cell expansion through dramatic increases in both islet and β-cell size and number. Herein we present a comparative expression profiling of myrAkt1 transgenic islets that demonstrates the increased abundance of transcripts encoding proteins associated with growth, suppression of apoptosis, RNA processing, and metabolism. Although IGFBP5 is identified as a gene induced by Akt1 activation in the β-cell, Igfbp5 expression is not necessary for myrAkt1 to augment β-cell size or mass in vivo. However, in the absence of Igfbp5, mice demonstrate an increase in size and mild glucose intolerance. This is accentuated during diet-induced obesity, when Igfbp5-deficient mice have increased adiposity compared with wild-type mice on the same diet. These studies reveal a novel role for Igfbp5 in the control of growth and metabolism.

Original languageEnglish (US)
Pages (from-to)178-192
Number of pages15
JournalMolecular Endocrinology
Volume24
Issue number1
DOIs
StatePublished - Jan 2010

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Insulin-Like Growth Factor Binding Protein 5
Insulin-Like Growth Factor I
Growth
Islets of Langerhans
Cell Size
Insulin
Diet
Insulin-Like Growth Factor Binding Proteins
Critical Pathways
Glucose Intolerance
Protein-Serine-Threonine Kinases
Adiposity
Cell Survival
Proteins
Obesity
Cell Count
Maintenance
RNA
Apoptosis
Glucose

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Gleason, C. E., Ning, Y., Cominski, T. P., Gupta, R. K., Kaestner, K. H., Pintar, J. E., & Birnbaum, M. J. (2010). Role of Insulin-Like Growth Factor-Binding Protein 5 (IGFBP5) in Organismal and Pancreatic β-Cell Growth. Molecular Endocrinology, 24(1), 178-192. https://doi.org/10.1210/me.2009-0167

Role of Insulin-Like Growth Factor-Binding Protein 5 (IGFBP5) in Organismal and Pancreatic β-Cell Growth. / Gleason, Catherine E.; Ning, Yun; Cominski, Tara P.; Gupta, Rana K; Kaestner, Klaus H.; Pintar, John E.; Birnbaum, Morris J.

In: Molecular Endocrinology, Vol. 24, No. 1, 01.2010, p. 178-192.

Research output: Contribution to journalArticle

Gleason, CE, Ning, Y, Cominski, TP, Gupta, RK, Kaestner, KH, Pintar, JE & Birnbaum, MJ 2010, 'Role of Insulin-Like Growth Factor-Binding Protein 5 (IGFBP5) in Organismal and Pancreatic β-Cell Growth', Molecular Endocrinology, vol. 24, no. 1, pp. 178-192. https://doi.org/10.1210/me.2009-0167
Gleason, Catherine E. ; Ning, Yun ; Cominski, Tara P. ; Gupta, Rana K ; Kaestner, Klaus H. ; Pintar, John E. ; Birnbaum, Morris J. / Role of Insulin-Like Growth Factor-Binding Protein 5 (IGFBP5) in Organismal and Pancreatic β-Cell Growth. In: Molecular Endocrinology. 2010 ; Vol. 24, No. 1. pp. 178-192.
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