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Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice.
Growth Horm IGF Res. 2011 Aug; 21(4):205-11.GH

Abstract

OBJECTIVE

Very preterm birth is associated with a high risk of morbidity. Infants born very preterm have low serum levels of insulin-like growth factor I (IGF-I), that further decrease after birth. IGF-I is essential for brain development and low serum levels have been associated with retinopathy of prematurity. The present study aimed to investigate the effects of prolonged administration of a low dose of rhIGF-I/rhIGFBP-3 on glucose levels and total body weight, as well as liver, spleen and brain weights, and gray and subcortical white matter in newborn mice.

DESIGN

The study was performed as three different trials. In all experiments C57BL/6N mice were injected with a rhIGF-I/rhIGFBP-3 complex or saline. In the first experimental trial, blood glucose levels were assessed 30 min, 1 h, 1.5 h, 3 h, 6 h, 24 h and 48 h after the rhIGF-I/rhIGFBP-3 or saline injection on postnatal day (PND) 6. In the second trial, mice were injected daily from PND 3 to 11 and sacrificed on PND 12 for analysis of IGF-I serum levels. In the third trial, body and organ weights and effects on gray and white matter were assessed on PND 18 after PND 3-11 treatments as above. Effects on gray and white matter were measured using immunoreactivity for microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), neurofilament and oligodendrocyte lineage transcription factor 2 (Olig2).

RESULTS

Blood glucose levels were unchanged in the rhIGF-I/rhIGFBP-3-treated group compared to baseline. In the control group glucose levels increased 30 min after the second saline injection; levels were not elevated at the subsequent time point. Three hours after the rhIGF-I/rhIGFBP-3 or saline, glucose levels were lower in rhIGF-I/rhIGFBP-3-treated animals than in saline treated (p=0.026). At PND 18, total body weight was higher in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.05), but there were no differences between groups in brain, liver or spleen weights. No differences in gray matter area were found between groups. Analyses of white matter markers showed an increased number of Olig2-positive cells in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.001). There were no differences between groups in terms of MBP, CNPase or neurofilament immunoreactivity.

CONCLUSIONS

Prolonged administration of rhIGF-I/rhIGFBP-3 did not have a negative impact on blood glucose levels and was beneficial for total body growth.

Authors+Show Affiliations

Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. gunnel.hellgren@vgregion.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21696987

Citation

Hellgren, Gunnel, et al. "Safety Aspects of Longitudinal Administration of IGF-I/IGFBP-3 Complex in Neonatal Mice." Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, vol. 21, no. 4, 2011, pp. 205-11.
Hellgren G, Han W, Wang X, et al. Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice. Growth Horm IGF Res. 2011;21(4):205-11.
Hellgren, G., Han, W., Wang, X., Löfqvist, C., Hagberg, H., Mallard, C., & Hellström, A. (2011). Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice. Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society, 21(4), 205-11. https://doi.org/10.1016/j.ghir.2011.05.006
Hellgren G, et al. Safety Aspects of Longitudinal Administration of IGF-I/IGFBP-3 Complex in Neonatal Mice. Growth Horm IGF Res. 2011;21(4):205-11. PubMed PMID: 21696987.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety aspects of longitudinal administration of IGF-I/IGFBP-3 complex in neonatal mice. AU - Hellgren,Gunnel, AU - Han,Wei, AU - Wang,Xiaoyang, AU - Löfqvist,Chatarina, AU - Hagberg,Henrik, AU - Mallard,Carina, AU - Hellström,Ann, Y1 - 2011/06/21/ PY - 2010/08/26/received PY - 2011/05/13/revised PY - 2011/05/13/accepted PY - 2011/6/24/entrez PY - 2011/6/24/pubmed PY - 2011/12/13/medline SP - 205 EP - 11 JF - Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society JO - Growth Horm IGF Res VL - 21 IS - 4 N2 - OBJECTIVE: Very preterm birth is associated with a high risk of morbidity. Infants born very preterm have low serum levels of insulin-like growth factor I (IGF-I), that further decrease after birth. IGF-I is essential for brain development and low serum levels have been associated with retinopathy of prematurity. The present study aimed to investigate the effects of prolonged administration of a low dose of rhIGF-I/rhIGFBP-3 on glucose levels and total body weight, as well as liver, spleen and brain weights, and gray and subcortical white matter in newborn mice. DESIGN: The study was performed as three different trials. In all experiments C57BL/6N mice were injected with a rhIGF-I/rhIGFBP-3 complex or saline. In the first experimental trial, blood glucose levels were assessed 30 min, 1 h, 1.5 h, 3 h, 6 h, 24 h and 48 h after the rhIGF-I/rhIGFBP-3 or saline injection on postnatal day (PND) 6. In the second trial, mice were injected daily from PND 3 to 11 and sacrificed on PND 12 for analysis of IGF-I serum levels. In the third trial, body and organ weights and effects on gray and white matter were assessed on PND 18 after PND 3-11 treatments as above. Effects on gray and white matter were measured using immunoreactivity for microtubule-associated protein-2 (MAP-2), myelin basic protein (MBP), 2',3'-cyclic nucleotide 3' phosphodiesterase (CNPase), neurofilament and oligodendrocyte lineage transcription factor 2 (Olig2). RESULTS: Blood glucose levels were unchanged in the rhIGF-I/rhIGFBP-3-treated group compared to baseline. In the control group glucose levels increased 30 min after the second saline injection; levels were not elevated at the subsequent time point. Three hours after the rhIGF-I/rhIGFBP-3 or saline, glucose levels were lower in rhIGF-I/rhIGFBP-3-treated animals than in saline treated (p=0.026). At PND 18, total body weight was higher in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.05), but there were no differences between groups in brain, liver or spleen weights. No differences in gray matter area were found between groups. Analyses of white matter markers showed an increased number of Olig2-positive cells in rhIGF-I/rhIGFBP-3-treated mice compared with controls (p<0.001). There were no differences between groups in terms of MBP, CNPase or neurofilament immunoreactivity. CONCLUSIONS: Prolonged administration of rhIGF-I/rhIGFBP-3 did not have a negative impact on blood glucose levels and was beneficial for total body growth. SN - 1532-2238 UR - https://www.unboundmedicine.com/medline/citation/21696987/Safety_aspects_of_longitudinal_administration_of_IGF_I/IGFBP_3_complex_in_neonatal_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-6374(11)00056-6 DB - PRIME DP - Unbound Medicine ER -