Sex-specific regulation of body size and bone slenderness by the acid labile subunit

Courtland, Hayden William; DeMambro, Victoria; Maynard, Jane A; Sun, Hui; Elis, Sébastien; Rosen, Clifford J.; Yakar, Shoshana

doi:10.1002/jbmr.94

Cited by 31 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lack of ternary complex formation due to ALS deletion was associated with increased adipogenesis from bone marrowderived mesenchymal stromal cells in culture, whereas recombinant ALS inhibited adipogenesis (43). Although ALS-deficient mice had normal body composition and insulin sensitivity (45), humans with ALS deficits are insulinresistant (46,47) and may be obese (47). Therefore, the lack of ternary complex formation of the mutant hIGFBP-3 could explain adiposity and insulin resistance in PGKmutBP3 mice.…”

Section: Discussionmentioning

confidence: 96%

Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

et al. 2014

View full text Add to dashboard Cite

We have reported a reduction of insulin secretion and glucose intolerance in young mice overexpressing human IGFBP-3 (phosphoglycerate kinase [PGK]BP3) or its mutant Gly56/Gly80/Gly81-IGFBP-3 (PGKmutBP3) under the PGK promoter. Here, we investigated changes in glucose and lipid homeostasis with age in PGKBP3 and PGKmutBP3 mice compared with wild-type mice. Body weight, glucose tolerance, insulin tolerance, visceral fat, interscapular brown adipose tissue (BAT), serum lipids, and pancreas histology were examined at age 3, 6, and 12 months. Murine IGFBP-3 was similar in all mouse genotypes and decreased with age in parallel with total IGF-1. Visceral fat and BAT masses increased in PGKmutBP3 mice, but not in PGKBP3 mice. Glucose tolerance was impaired in both PGKBP3 and PGKmutBP3 mice. However, PGKBP3 mice had increased expression of uncoupling protein-1 in BAT and reduced adiposity, and continued to have smaller pancreatic β-cell mass and reduced insulin secretion through age 12 months. In contrast, PGKmutBP3 mice developed insulin resistance with age in association with pancreatic β-cell hyperplasia, impaired expression of uncoupling protein-1 in BAT, and increased adiposity. In addition, both PGKBP3 and PGKmutBP3 mice had elevated glycerol in the circulation, but only PGKBP3 mice had elevated free fatty acids and only PGKmutBP3 mice had elevated triglycerides. Estimated free IGF-1 did not increase with age in transgenic mice, as it did in wild-type mice. Thus, overexpression of human IGFBP-3 or its mutant devoid of IGF binding ability leads to glucose intolerance with, however, different effects on insulin secretion, insulin sensitivity, and lipid homeostasis in aging mice.

show abstract

Section: Discussionmentioning

confidence: 96%

Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Data from experimental animals provide stronger evidence for this relationship. Genetically modified animals that do not make IGF-I in the liver have significantly reduced cortical bone volume, periosteal circumference, and cross-sectional area [50, 51]. Thus, in vivo animal models demonstrate that systemic IGF-I is necessary for bone modeling (net gain) and mineralization [52].…”

Section: Discussionmentioning

confidence: 99%

Serum sclerostin decreases following 12months of resistance- or jump-training in men with low bone mass

Hinton

Nigh

Thyfault

2017

Bone

View full text Add to dashboard Cite

Purpose We previously reported that 12 mo of resistance training (RT, 2×/wk, N= 19) or jump training (JUMP, 3×/wk, N= 19) increased whole body and lumbar spine BMD and increased serum bone formation markers relative to resorption in physically active (≥4 hr/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine. The purpose of this secondary analysis was to examine the effects of the RT or JUMP intervention on potential endocrine mediators of the exercise effects on bone, specifically IGF-I, PTH and sclerostin. Methods Fasting blood samples were collected after a 24-h period of no exercise at baseline and after 12 months of RT or JUMP. IGF-I, PTH and sclerostin were measured in serum by ELISA. The effects of RT or JUMP on IGF-I, PTH and sclerostin were evaluated using 2×2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB. Results Sclerostin concentrations in serum significantly decreased and IGF-I significantly increased after 12 mo of RT or JUMP; while PTH remained unchanged. Conclusion The beneficial effects of long-term, progressive-intensity RT or JUMP on BMD in moderately active men with low bone mass are associated with decreased sclerostin and increased IGF-I.

show abstract

“…Whether a low bone mineralization is due to ALS deficiency per se or delayed bone maturation or a genetic background deserves further investigation. In favor of a role of ALS deficiency in contributing to a lower bone mineral density is the decreased bone mineral density reported in the Igfals knockout mice, where the decrease is likely due to the low IGF-I concentrations [23]. …”

Section: Discussionmentioning

confidence: 99%

A Novel Homozygous Mutation of the <b><i>IGFALS</i></b> Gene in a Female Adolescent: Indirect Evidence for a Contributing Role of the Circulating IGF-I Pool in the Pubertal Growth Spurt

et al. 2014

View full text Add to dashboard Cite

Background: Mutations of the IGFALS gene have been reported since 2004 in 24 patients, but only 5 of these are females. Case Report: We describe a 14.7-year-old female of a consanguineous Moroccan family with growth retardation and normal-onset but slow progression of puberty without manifest pubertal height gain. Results: At age 3.2 years, the patient's height was 85.5 cm (-2.9 SDS) and her weight 9.9 kg (-2.9 SDS) with a head circumference of 44.5 cm (-3.3 SDS). Serum IGF-I and IGFBP-3 concentrations were low with normal basal and stimulated growth hormone (GH) levels. An IGF-I generation test confirmed a lack of response to GH administration. While onset of puberty occurred at a normal age, no significant pubertal growth acceleration was observed despite progression of breast development. Sequencing of the IGFALS gene revealed a novel homozygous frameshift mutation (c.1291delT) with a stop codon (p.W431GfsX10) leading to undetectable serum levels of acid-labile subunit. Conclusion: We report the phenotype of an adolescent girl with primary IGF-I deficiency due to a novel homozygous mutation of the IGFALS gene, who presented with growth delay, normal pubertal onset with slow progression and no pubertal growth acceleration indirectly suggesting a contributing role of the circulating IGF-I pool in the pubertal growth spurt.

show abstract

Sex-specific regulation of body size and bone slenderness by the acid labile subunit

Cited by 31 publications

References 31 publications

Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

Serum sclerostin decreases following 12months of resistance- or jump-training in men with low bone mass

A Novel Homozygous Mutation of the <b><i>IGFALS</i></b> Gene in a Female Adolescent: Indirect Evidence for a Contributing Role of the Circulating IGF-I Pool in the Pubertal Growth Spurt

Contact Info

Product

Resources

About