Role of insulin-like growth factor-binding protein 5 (IGFBP5) in organismal and pancreatic beta-cell growth.
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.
Gleason
Catherine E
CE
University of Pennsylvania School of Medicine, Department of Medicine, Institute for Diabetes, Obesity, and Metabolism, Philadelphia, Pennsylvania 19104, USA.
Ning
Yun
Y
Cominski
Tara P
TP
Gupta
Rana
R
Kaestner
Klaus H
KH
Pintar
John E
JE
Birnbaum
Morris J
MJ
D050154:Adiposity / Q000235:genetics; D000818:Animals; D049628:Body Size / Q000235:genetics; D002460:Cell Line; D048429:Cell Size; D053595:Embryonic Stem Cells / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D018149:Glucose Intolerance / Q000235:genetics; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size; D009928:Organ Specificity; D011247:Pregnancy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation
D018975:Insulin-Like Growth Factor Binding Protein 5; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt