Document Detail

Signaling cross talk between growth hormone (GH) and insulin-like growth factor-I (IGF-I) in pancreatic islet β-cells.
MedLine Citation:
PMID:  22034225     Owner:  NLM     Status:  MEDLINE    
Dysfunction and destruction of pancreatic islet β-cells is a hallmark of diabetes. Better understanding of cell signals regulating β-cell growth and antiapoptosis will allow development of therapeutic strategies for diabetes by preservation and expansion of β-cell mass. GH and IGF-I share a complicated physiological relationship and have both been implicated in β-cell function. GH and IGF-I exert their biological effects through binding to respective receptors (GHR and IGF-IR) and subsequently engaging downstream signaling pathways. However, their collaborative roles in modulation of β-cell mass and the underlying molecular mechanisms remain poorly understood. In this study, we demonstrate that cultured β-cells are appealing systems for investigating potential GH-IGF-I signaling cross talk. We uncover that GH specifically promotes formation of a protein complex containing GHR, Janus kinase 2 (a nonreceptor kinase coupled to GH/GHR signaling), and IGF-IR. More importantly, GH and IGF-I synergistically activate both signal transducer and activator of transcription 5 and Akt pathways. Concomitantly, β-cells proliferate more robustly and are better protected from serum deprivation-induced apoptosis when exposed to GH and IGF-I in combination vs. GH or IGF-I alone. The augmented proliferative effects by GH and IGF-I are confirmed in isolated islets. Taken together, our findings strongly suggest that there exists a novel signaling relationship between GH/GHR and IGF-I/IGF-IR systems in β-cells, i.e. IGF-IR may serve as a proximal component of GH/GHR signaling, contributing to enhancement of β-cell mass and function. In support of this, IGF-IR knockdown in β-cells resulted in the desensitization of acute GH-induced signal transducer and activator of transcription 5 activation.
Fanxin Ma; Zhe Wei; Chunwei Shi; Yan Gan; Jia Lu; Stuart J Frank; James Balducci; Yao Huang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-10-27
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  25     ISSN:  1944-9917     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-11-28     Completed Date:  2012-03-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2119-33     Citation Subset:  IM    
Laboratory of Signal Transduction, Department of Obstetrics and Gynecology, St. Joseph’s Hospital and Medical Center, Phoenix, Arizona 85004, USA.
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MeSH Terms
Cell Proliferation
Cell Survival
Cells, Cultured
Enzyme Activation
Gene Knockdown Techniques
Growth Hormone / pharmacology,  physiology*
Insulin-Like Growth Factor I / pharmacology,  physiology*
Insulin-Secreting Cells / metabolism,  physiology*
Janus Kinase 2 / metabolism
Mice, Inbred C57BL
Protein Multimerization
RNA Interference
Receptor Cross-Talk*
Receptor, IGF Type 1 / genetics,  metabolism*
Receptors, Somatotropin / metabolism*
STAT5 Transcription Factor / metabolism
Signal Transduction
Grant Support
Reg. No./Substance:
0/Receptors, Somatotropin; 0/STAT5 Transcription Factor; 0/insulin-like growth factor-1, mouse; 67763-96-6/Insulin-Like Growth Factor I; 9002-72-6/Growth Hormone; EC, IGF Type 1; EC protein, mouse; EC Kinase 2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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