Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis

Taylor, Adam Michael; Bush, Anne; Thomson, A. D.; Oades, Patrick; Marchant, J L; Bruce-Morgan, C.; Holly, Jeff M.P.; Ahmed, Lasker S.; Dunger, David B.

doi:10.1136/adc.76.4.304

Cited by 62 publications

(65 citation statements)

References 44 publications

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“…Serum IGF-I levels were significantly lower in CF patients than in controls. At variance with previous studies this did not seem to be dependent on malnutrition or anorexia (9,14,28,29) as the BMI values of these patients were normal and similar to those of controls, and total serum protein concentration was normal. Other authors have hypothesized that low serum IGF-I concentrations could be dependent on insulin hyposecretion in CF.…”

Section: Discussioncontrasting

confidence: 85%

“…IGFBP-3 serum concentrations were similar in the patients and controls although they tended to be lower in patients with the most severe clinical state, and we did not find any relationship with insulin at variance with previously published data (28,29). This helps to explain why the IGF-I/IGFBP-3 molar ratios were similar in CF and healthy subjects.…”

Section: Discussionsupporting

confidence: 74%

“…Other authors have hypothesized that low serum IGF-I concentrations could be dependent on insulin hyposecretion in CF. Taylor et al (28) described a progressive reduction of IGF-I and IGFBP-3 related to declining BMI, and deteriorating pulmonary function, and suggested that progressive insulin deficiency might be contributing to this. Ripa et al (29) further supported this hypothesis by showing a high frequency of insulin hyposecretion with increased serum IGFBP-1 levels, normal IGF-I and reduced growth velocity in CF.…”

Section: Discussionmentioning

confidence: 99%

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Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

et al. 2006

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Objective: In inflammatory bowel diseases, increased serum interleukin (IL)-6 levels are associated with high serum insulin-like growth factor-binding protein 2 (IGFBP-2) levels, and cytokines modify the insulin-like growth factor (IGF)/IGFBP system in models in vitro. In cystic fibrosis (CF) the IGF/IGFBP system has not been extensively studied, and relationships with proinflammatory cytokines have not been explored. The aim of this study was to investigate the IGF/IGFBP system and verify changes dependent on IL-1b, IL-6, tumour necrosis factor a (TNFa), and insulin. Methods: Eighteen subjects with CF (mean age 26.6^1.1 years) and 18 controls, comparable for age, sex, and body mass index, were enrolled. Serum IGF-I, IGF-II, IGFBP-2, IGFBP-3, IL-1b, IL-6, TNFa, insulin and C-peptide were measured. Different molecular forms of IGFBP-2 and IGFBP-3 were investigated by Western immunoblotting. The patients were analysed as a whole and as two subgroups depending on established clinical criteria (Swachman -Kulczycki score). Results: Patients had higher serum concentrations of IL-1b, IL-6, TNFa and IGFBP-2 than controls. Serum concentrations of IGF-I and IGF-II were significantly lower and insulin and C-peptide levels significantly increased in CF compared with healthy controls whereas IGFBP-3 serum concentrations were similar, with comparable IGF-I/IGFBP-3 and decreased IGF-I/IGFBP-2 and IGF-II/IGFBP-2 molar ratios. From correlation analysis we detected a significant positive correlation between IGFBP-2 and IL-6 and a negative correlation between IGFBP-2 and IGFBP-3. Conclusions: Our findings suggest that inflammation is an important modulator of the IGF/IGFBP system with an overall reduction in IGF bioactivity in CF.European Journal of Endocrinology 154 47-52

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Section: Discussioncontrasting

confidence: 85%

Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

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Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

et al. 2006

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“…To determine whether rhIGFBP-3 treatment affected systemic levels of Igf-I or Igfbp-3, the serum levels of these proteins were measured. As shown in Figure 5A, Igf-I was lower in serum from CF versus non-CF mice (p ϭ 0.003) as has been reported for CF patients (17) and CF mice (18), whereas Igfbp-3 levels were significantly increased (p ϭ 0.002). Serum levels of Igfbp-3 have not been reported for CF mice, whereas in CF patients, these measures have been shown to be lower (17) or unaltered (19); neither measure was significantly altered by rhIGFBP-3 treatment.…”

Section: Expression Of Igf Pathway Genes Is Altered In Intestines Of supporting

confidence: 76%

IGF Binding Protein-3 Treatment Alters Intestinal Cell Proliferation But Not Body Weight of Adult Cystic Fibrosis Transmembrane Conductance Regulator Deficient Mice

Canale-Zambrano

Haston

2011

Pediatr Res

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ABSTRACT:The intestinal phenotype of cystic fibrosis (CF) transmembrane conductance regulator deficient mice includes altered cell homeostasis and a distended crypt-villus axis, which, in previous work, was inversely proportional to body weight. To investigate this correlation, herein, we treated CF mice with IGF binding protein-3 (IGFBP-3), a protein which, as it has potent effects on cell proliferation and apoptosis, we hypothesized would alter the intestinal cell homeostasis, and assessed body weight. Six-week-old C57BL/ 6JxBALB F2 CF and WT mice received recombinant human IGFBP-3 (rhIGFBP-3, 20 mg/kg) or vehicle treatment, and weight gain, serum protein levels, and intestinal histology were assessed. Administration of rhIGFBP-3 to CF mice significantly increased the number of Igfbp-3 positive cells in the intestine and partially reversed the hyperproliferative phenotype of intestinal crypts and muscularis externa, while not affecting apoptosis. Serum Igfbp-3 levels were increased, and Igf-I, albumin, and triglycerides measures were decreased in CF compared with WT mice. rhIGFBP-3 treatment significantly increased serum albumin and triglycerides but did not affect weight gain in CF mice. We have identified rhIGFBP-3 treatment to reduce intestinal cell proliferation, resulting in decreases in crypt depth and muscularis externa thickness in CF mice.

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“…Several studies have shown significant deficits of Igf-1 in CF patients (27)(28)(29). The behavior of GH in CF patients is more equivocal, with studies showing higher, normal, or lower levels of the hormone [reviewed in (28)].…”

Section: Growth In Cystic Fibrosis Micementioning

confidence: 99%

Mouse as a Model of Growth Retardation in Cystic Fibrosis

et al. 2006

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Cystic fibrosis (CF) is an autosomal recessive disease that results in lung failure and premature death. A long recognized symptom of CF is growth failure, which is clinically relevant because it correlates with the severity of lung disease. We describe growth retardation in a mouse model of CF and discuss its potential for modeling certain aspects of human growth retardation. Mice with a null mutation in Cftr (cystic fibrosis transmembrance conductance regulator) were compared with wild-type (WT) mice at 31, 45, and 84 d of age. CF mice were severely growth retarded in weight and length compared with wild-type controls. Serum insulin like growth factor I (Igf-1) was lower in CF mice by 31-55% (depending on age and sex) and it significantly correlated with the size of mice after controlling for gender, age, and Cftr genotype. There was a marginally significant deficiency of serum growth hormone (Gh) in CF females, but not males. Our findings were consistent with models of an energy deficit in rodents. We, therefore, assessed food intake and found no difference between CF and WT mice, suggesting that CF mice had a malabsorption-mediated energy deficit. We argue that CF mice are suited to study the effects of intestinal disease on growth as well as other proposed growth-modulating processes. (Pediatr Res 59: [191][192][193][194][195] 2006)

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Relation between insulin-like growth factor-I, body mass index, and clinical status in cystic fibrosis

Cited by 62 publications

References 44 publications

Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

Inflammation is a modulator of the insulin-like growth factor (IGF)/IGF-binding protein system inducing reduced bioactivity of IGFs in cystic fibrosis

IGF Binding Protein-3 Treatment Alters Intestinal Cell Proliferation But Not Body Weight of Adult Cystic Fibrosis Transmembrane Conductance Regulator Deficient Mice

Mouse as a Model of Growth Retardation in Cystic Fibrosis

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