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Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.


ABSTRACT: A family of IGF-binding proteins (IGFBP) exerts biological actions both dependent on and 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 beta-cell, the insulin/IGF-I signaling pathway is critical for normal and adaptive maintenance of beta-cell mass. Expression of myrAkt1, an activated form of Akt, in the endocrine pancreas drives beta-cell expansion through dramatic increases in both islet and beta-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 beta-cell, Igfbp5 expression is not necessary for myrAkt1 to augment beta-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.

SUBMITTER: Gleason CE 

PROVIDER: S-EPMC2802899 | biostudies-other | 2010 Jan

REPOSITORIES: biostudies-other

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Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.

Gleason Catherine E CE   Ning Yun Y   Cominski Tara P TP   Gupta Rana R   Kaestner Klaus H KH   Pintar John E JE   Birnbaum Morris J MJ  

Molecular endocrinology (Baltimore, Md.) 20091106 1


A family of IGF-binding proteins (IGFBP) exerts biological actions both dependent on and 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 beta-cell, the insulin/IGF-I signaling pathway is critical for normal and adaptive maintenance of beta-cell mass. Expressio  ...[more]

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