Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

Mark P Rogan; Leah R Reznikov; Alejandro A Pezzulo; Nicholas D Gansemer; Melissa Samuel; Randall S Prather; Joseph Zabner; Douglas C Fredericks; Paul B McCray; Michael J Welsh; David A Stoltz

doi:10.1073/pnas.1015281107

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Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

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Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth

Mark P Rogan, Leah R Reznikov, Alejandro A Pezzulo, Nicholas D Gansemer, Melissa Samuel, Randall S Prather, Joseph Zabner, Douglas C Fredericks, Paul B McCray, Michael J Welsh, …

Proceedings of the National Academy of Sciences - PNAS, Vol.107(47), pp.20571-20575

11/23/2010

DOI: 10.1073/pnas.1015281107

PMCID: PMC2996661

PMID: 21059918

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Abstract

People with cystic fibrosis (CF) exhibit growth defects. That observation has been attributed, in part, to decreased insulin-like growth factor 1 (IGF1) levels, and the reduction has been blamed on malnutrition and pulmonary inflammation. However, patients with CF already have a reduced weight at birth, a manifestation not likely secondary to poor nutrition or inflammation. We found that, like humans, CF pigs were smaller than non-CF littermates and had lower IGF1 levels. To better understand the basis of IGF1 reduction, we studied newborn pigs and found low IGF1 levels within 12 h of birth. Moreover, humerus length and bone mineral content were decreased, consistent with less IGF1 activity in utero. These findings led us to test newborn humans with CF, and we found that they also had reduced IGF1 levels. Discovering lower IGF1 levels in newborn pigs and humans indicates that the decrease is not solely a consequence of malnutrition or pulmonary inflammation and that loss of cystic fibrosis transmembrane conductance regulator function has a more direct effect. Consistent with this hypothesis, we discovered reduced growth hormone release in organotypic pituitary slice cultures of newborn CF pigs. These findings may explain the long-standing observation that CF newborns are smaller than non-CF babies and why some patients with good clinical status fail to reach their growth potential. The results also suggest that measuring IGF1 levels might be of value as a biomarker to predict disease severity or the response to therapeutics. Finally, they raise the possibility that IGF1 supplementation beginning in infancy might be beneficial in CF.

Biological Sciences

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Title: Subtitle: Pigs and humans with cystic fibrosis have reduced insulin-like growth factor 1 (IGF1) levels at birth
Creators: Mark P Rogan - Departments of
Leah R Reznikov - Departments of
Alejandro A Pezzulo - Departments of
Nicholas D Gansemer - Departments of
Melissa Samuel - Division of Animal Sciences
Randall S Prather - Division of Animal Sciences
Joseph Zabner - Departments of
Douglas C Fredericks - Orthopedics and Rehabilitation
Paul B McCray - Pediatrics, and
Michael J Welsh - Departments of
David A Stoltz - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.107(47), pp.20571-20575
DOI: 10.1073/pnas.1015281107
PMID: 21059918
PMCID: PMC2996661
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 11/23/2010
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Orthopedics and Rehabilitation; Craniofacial Anomalies Research Center; Neurosurgery; Internal Medicine
Record Identifier: 9984015212902771

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