The Role of IGF-I, IGF-II, and IGFBP-3 in Male Cognitive Aging and Dementia Risk: The Caerphilly Prospective Study

2014 ◽  
Vol 41 (3) ◽  
pp. 867-875 ◽  
Author(s):  
Christopher J. Green ◽  
Jeffrey M.P. Holly ◽  
Antony Bayer ◽  
Mark Fish ◽  
Shah Ebrahim ◽  
...  
Keyword(s):  
Prospective Study ◽  
Cognitive Aging ◽  
Dementia Risk ◽  
Igf I ◽  
Igfbp 3

scholarly journals Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2164-2173 ◽  
Author(s):  
Woo-Young Kim ◽  
Mi-Jung Kim ◽  
Hojin Moon ◽  
Ping Yuan ◽  
Jin-Soo Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Tumor ◽  
Binding Protein ◽  
Cancer Development ◽  
Lung Carcinogenesis ◽  
Tobacco Carcinogen ◽  
Igf I ◽  
The Impact ◽  
Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

scholarly journals Growth hormone-binding protein is directly and IGFBP-3 is inversely associated with risk of female breast cancer

2007 ◽  
Vol 156 (2) ◽  
pp. 187-194 ◽  
Author(s):  
Kalliopi Pazaitou-Panayiotou ◽  
Theodore Kelesidis ◽  
Iosif Kelesidis ◽  
Athina Kaprara ◽  
Jennifer Blakeman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Breast Cancer Risk ◽  
Female Breast Cancer ◽  
Cancer Risk Factors ◽  
Female Breast ◽  
Igf I ◽  
Breast Cancer Risk Factors ◽  
Igfbp 3

Objective: Several components of the GH and IGF systems have been implicated in the development of malignancies. All components of these hormonal systems have never been jointly evaluated in female breast cancer, and previous studies have not examined the role of IGF-binding proteins (IGFBP-4, IGFBP-6) or GH-binding protein (GHBP). Design: Hospital-based case–control study. Methods: In this sample of primarily postmenopausal women, we obtained serum measures of IGF-I, IGF-II, and binding proteins IGFBP-1, IGFBP-3, IGFBP-4, IGFBP-6, as well as GHBP, insulin, and leptin from 74 breast cancer cases and 76 control subjects. Results: In crude analyses, we found lower age-standardized mean IGF-I, IGFBP-3, IGFBP-4, IGFBP-6, and higher IGFBP-1 and GHBP in breast cancer cases when compared with controls. Multivariate models mutually adjusted for other GH–IGF system components and classical breast cancer risk factors demonstrated an inverse association between IGFBP-3 and risk of breast cancer (odds ratio (OR) = 0.2, P < 0.01) and a direct association between GHBP and disease risk (OR = 3.3, P < 0.01). No significant associations were detected in multivariate analyses among IGF-I, IGF-II or IGFBP-1, IGFBP-4, IGFBP-6 with risk of breast cancer, indicating that these factors may not have effects independent of and/or comparable with IGFBP-3 and GHBP. Conclusions: These results support a protective role of IGFBP-3 and demonstrate for the first time an increased risk of breast cancer with higher GHBP, after accounting for variation in IGFs, IGFBPs, and classical breast cancer risk factors.

The role of intraindividual cognitive variability in posttraumatic stress syndromes and cognitive aging: a literature search and proposed research agenda

2020 ◽  
pp. 1-11
Author(s):  
Lauren A. Rutter ◽  
Ipsit V. Vahia ◽  
Eliza Passell ◽  
Brent P. Forester ◽  
Laura Germine
Keyword(s):  
Posttraumatic Stress ◽  
Cognitive Aging ◽  
Research Agenda ◽  
Psychiatric Symptoms ◽  
Empirical Studies ◽  
Severe Trauma ◽  
Dementia Risk ◽  
Cognitive Variability ◽  
Intraindividual Cognitive Variability

Abstract Objectives: Cognitive impairments are directly related to severity of symptoms and are a primary cause for functional impairment. Intraindividual cognitive variability likely plays a role in both risk and resiliency from symptoms. In fact, such cognitive variability may be an earlier marker of cognitive decline and emergent psychiatric symptoms than traditional psychiatric or behavioral symptoms. Here, our objectives were to survey the literature linking intraindividual cognitive variability, trauma, and dementia and to suggest a potential research agenda. Design: A wide body of literature suggests that exposure to major stressors is associated with poorer cognitive performance, with intraindividual cognitive variability in particular linked to the development of posttraumatic stress disorder (PTSD) in the aftermath of severe trauma. Measurements: In this narrative review, we survey the empirical studies to date that evaluate the connection between intraindividual cognitive variability, PTSD, and pathological aging including dementia. Results: The literature suggests that reaction time (RT) variability within an individual may predict future cognitive impairment, including premature cognitive aging, and is significantly associated with PTSD symptoms. Conclusions: Based on our findings, we argue that intraindividual RT variability may serve as a common pathological indicator for trauma-related dementia risk and should be investigated in future studies.

Relationships Between Levels of Leptin and Hematological Parameters in Healthy Term Infants

2001 ◽  
Vol 14 (8) ◽  
Author(s):  
Esin Koç ◽  
Aysun Bideci ◽  
Peyami Cinaz ◽  
Ebru Ergenekon ◽  
Yıldız Atalay
Keyword(s):  
Hematological Parameters ◽  
Serum Concentrations ◽  
Term Infants ◽  
Positive Correlation ◽  
Blood Hemoglobin ◽  
Igf I ◽  
The Mean ◽  
Igfbp 3

AbstractIn order to evaluate the role of leptin in neonatal hematological parameters, we studied the serum concentrations of leptin in relation to blood hemoglobin, leukocyte and platelet values in 30 healthy term infants. We also studied the serum concentrations of IGF-I and IGFBP-3 in relation to leptin concentrations. The mean concentrations of leptin, IGF-I and IGFBP-3 were 1.63 ± 1.09, 24.65 ± 10.04 and 976.05 ± 214.50, respectively, at birth. A positive correlation was observed between leptin concentrations and birth weights of the infants. As no relationship could be found between concentrations of leptin and blood hemoglobin, leukocyte and platelet values, we could not determine any involvement of leptin in the regulation of physiologial hemoglobin, leukocyte and platelet concentrations at birth.

scholarly journals The Role of the Insulin-Like Growth Factors and Their Binding Proteins in Glucose Homeostasis

2003 ◽  
Vol 4 (4) ◽  
pp. 213-224 ◽  
Author(s):  
Liam J. Murphy
Keyword(s):  
Growth Factors ◽  
Glucose Homeostasis ◽  
Binding Proteins ◽  
Biological Fluids ◽  
Short Term ◽  
High Affinity ◽  
Igf I ◽  
Igfbp 3 ◽  
Insulin Like Growth Factors

The insulin like growth factors (IGF-I and -II) are structurally and functionally related to insulin. While insulin is a key regulator of glucose homeostasis over the short term, emerging evidence suggests that the IGFs are involved in the longer term glucose homeostasis, possibly by modulating insulin sensitivity. Unlike insulin, the IGFs are present in most biological fluids as complexes with high affinity binding proteins, the insulin-like growth factor binding proteins (IGFBPs). The IGFBPs regulate the bioavailability of the IGFs. Of the six IGFBPs identified there is evidence from studies in transgenic mice that both IGFBP-1 and IGFBP-3 may have a role in glucose regulation.

scholarly journals Steroid Receptor Coactivator 3 Maintains Circulating Insulin-Like Growth Factor I (IGF-I) by Controlling IGF-Binding Protein 3 Expression

2008 ◽  
Vol 28 (7) ◽  
pp. 2460-2469 ◽  
Author(s):  
Lan Liao ◽  
Xian Chen ◽  
Shu Wang ◽  
Albert F. Parlow ◽  
Jianming Xu
Keyword(s):  
Vitamin D ◽  
Growth Factor ◽  
Insulin Like Growth Factor ◽  
Steroid Receptor Coactivator ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

ABSTRACT Steroid receptor coactivator 3 (SRC-3/AIB1/ACTR/NCoA-3) is a transcriptional coactivator for nuclear receptors including vitamin D receptor (VDR). Growth hormone (GH) regulates insulin-like growth factor I (IGF-I) expression, and IGF-I forms complexes with acid-labile subunit (ALS) and IGF-binding protein 3 (IGFBP-3) to maintain its circulating concentration and endocrine function. This study demonstrated that the circulating IGF-I was significantly reduced in SRC-3−/− mice with the C57BL/6J background. However, SRC-3 deficiency affected neither GH nor ALS expression. The low IGF-I level in SRC-3−/− mice was not due to the failure of IGF-I mRNA and protein synthesis but was a consequence of rapid degradation. The rapid IGF-I degradation was associated with drastically reduced IGFBP-3 levels. Because IGF-I and IGFBP-3 stabilize each other, SRC-3−/− mice were crossbred with the liver-specific transthyretin (TTR)-IGF-I transgenic mice to assess the relationship between reduced IGF-I and IGFBP-3. In SRC-3−/−/TTR-IGF-I mice, the IGF-I level was significantly increased over that in SRC-3−/− mice, but the IGFBP-3 level failed to increase proportionally, indicating that the low IGFBP-3 level is a responsible factor that limits the IGF-I level in SRC-3−/− mice. Furthermore, IGFBP-3 mRNA was reduced in SRC-3−/− mice. The IGFBP-3 promoter activity induced by vitamin D, through VDR, was diminished in SRC-3−/− cells, suggesting an important role of SRC-3 in VDR-mediated transactivation of the IGFBP-3 gene. In agreement with the role of SRC-3 in VDR function, the expression of several VDR target genes was also reduced in SRC-3−/− mice. Therefore, SRC-3 maintains IGF-I in the circulation through enhancing VDR-regulated IGFBP-3 expression.

scholarly journals Pre- and Postoperative Circulating IGF-I, IGFBP-3, and IGFBP-7 Levels in Relation to Endocrine Treatment and Breast Cancer Recurrence: A Nested Case-Control Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Ann H. Rosendahl ◽  
Sofie Björner ◽  
Maria Ygland Rödström ◽  
Karin Jirström ◽  
Signe Borgquist ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
Cancer Recurrence ◽  
Recurrence Risk ◽  
Breast Cancer Recurrence ◽  
Postoperative Changes ◽  
Igf I ◽  
Control Study ◽  
Igfbp 3

Insulin-like growth factor-I (IGF-I) and its binding proteins (BPs) have been associated with breast cancer risk, especially high IGF-I concentrations and the biologically active fraction estimated as the IGF-I/IGFBP-3 molar ratio. The relation of circulating IGF-I and IGFBP-3 concentrations with risk of breast cancer recurrence has been less documented. In addition a new member to a sub-group of the IGFBP-superfamily was recently identified, the low affinity IGFBP-7. To date, the role of systemic IGFBP-7 in breast cancer progression has not been investigated. Our purpose was to establish whether circulating IGF-I, IGFBP-3, and IGFBP-7 levels are related to recurrence-risk in breast cancer. A case-control study was nested within the population-based BCBlood cohort of 853 breast cancer patients diagnosed 2002–2010 in Sweden and followed through 2012. In total, 95 patients with recurrence and 170 controls were matched on age and tumor characteristics. Plasma IGF analytes and tumor membrane IGF-I receptor (IGF-IRm) positivity were analyzed and recurrence-risk was evaluated with conditional logistic regression. Preoperative tertiles of IGF-I and IGFBP-3 were both positively associated with recurrence-risk, but not IGFBP-7. The trend was of borderline significance for IGF-I, T1:REF, T2 OR:1.6, T3 OR: 2.2 adjusted Ptrend=0.057 and significant for IGFBP-3 T1:REF, T2 OR:1.2, T3 OR: 2.1 adjusted Ptrend=0.042. The models were adjusted for age, anthropometric factors, smoking, and treatments. There was a significant interaction between IGFBP-7 and IGF-IRm positivity on recurrence, where the highest IGFBP-7 highest IGFBP-7 tertile conferred increased recurrence-risk in patients with IGF-IRm positive tumors but not in those with IGF-IRm negative tumors (Pinteraction=0.024). By the 1-year visit, age-adjusted IGF-I levels were reduced by 17% while IGFBP-3 and IGFBP-7 were stable. IGF-I levels were significantly reduced by radiotherapy in all patients and by tamoxifen in patients with ER+ tumors. Postoperative changes &gt;10% (n=208) in IGF-I, IGFBP-3, IGFBP-7, or the IGF-I/IGFBP-3 ratio did not predict recurrence after adjustment for preoperative levels, age, anthropometric factors, smoking, and treatments. In conclusion, this study suggests that preoperative IGF-I and IGFBP-3 levels, but not postoperative changes, might provide independent prognostic information and influence breast cancer recurrence. The role of IGFBP-7 in breast cancer merits further study.

scholarly journals The role of IGF binding protein-3 as a parameter of activity in acromegalic patients

1999 ◽  
pp. 145-148 ◽  
Author(s):  
I Halperin ◽  
R Casamitjana ◽  
L Flores ◽  
M Fernandez-Balsells ◽  
E Vilardell
Keyword(s):  
Binding Protein ◽  
Serum Levels ◽  
Glucose Load ◽  
Gh Secretion ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Normal Standard ◽  
Igfbp 3

OBJECTIVE: The production of insulin-like growth factor binding protein-3 (IGFBP-3), the main IGF-I binding protein, is regulated by GH, and its serum levels are increased in acromegaly. We investigated its potential value as a parameter of acromegaly activity or remission in comparison with IGF-I, taking GH suppression below 2 microg/l after glucose load as the normal standard. METHODS: Data from 40 acromegalic patients (12 males and 28 females, aged 28 to 79 years) were obtained retrospectively from stored samples. From these, 145 pairs of IGF-I/IGFBP-3 values were collected; in 67 of them, simultaneous measurement of GH after glucose loading allowed their classification as active or inactive acromegaly. Relationships between IGF-I, IGFBP-3 and GH after glucose load were assessed, as well as differences between IGF-I and IGFBP-3 levels in active and inactive acromegaly. RESULTS: Significant positive correlation between IGF-I and IGFBP-3 in 145 samples was observed (r=0.49, P<0. 0001). As for the 67 samples in which activity or remission could be defined in terms of GH after glucose load, 50 were active and 17 inactive. Both IGF-I and IGFBP-3 significantly correlated with minimum GH (r=0.53, P<0.0001 and r=0.41, P<0.001 respectively). For both parameters, significant differences of means between active and inactive cases were observed (623+/-296 vs 300+/-108 ng/ml, P<0.0001 for IGF-I, and 4.1+/-1.3 vs 3.2+/-0.9 microg/ml, P<0.006 for IGFBP-3). Yet, when comparing in individual cases their classification as active or inactive with the finding of normal or increased IGF-I and IGFBP-3, among active cases 16% appeared as normal according to IGF-I, and 50% appeared as normal in terms of IGFBP-3. Among inactive cases, 23.5% appeared as active according to IGF-I, while 17.5% appeared as active in terms of IGFBP-3. CONCLUSION: Even though IGFBP-3 reflects GH secretion, it offers no advantage over IGF-I in the assessment of acromegaly, and it may underestimate disease activity in acromegalic patients.

Role of IGF system of mitogens in the induction of fibroblast proliferation by keloid-derived keratinocytes in vitro

2003 ◽  
Vol 284 (4) ◽  
pp. C860-C869 ◽  
Author(s):  
Toan-Thang Phan ◽  
Ivor Jiun Lim ◽  
Boon Huat Bay ◽  
Robert Qi ◽  
Michael Thornton Longaker ◽  
...  
Keyword(s):  
Mrna Levels ◽  
Igf System ◽  
Normal Keratinocytes ◽  
Wound Healing Response ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Keloids are proliferative dermal growths representing a pathological wound-healing response. We report high proliferation rates in normal (NF) and keloid-derived fibroblasts (KF) cocultured with keloid-derived keratinocytes (KK). IGF binding protein (IGFBP)-3 mRNA and secreted IGFBP-3 in conditioned media were increased in NF cocultured with KK compared with NF but markedly reduced in KF cocultured with KK or normal keratinocytes (NK). IGFBP-2 and IGFBP-4 mRNA levels were elevated, whereas IGFBP-5 mRNA was decreased in KF cocultured with KK or NK. Significant increases in IGFBP-2 and -4 mRNA in KF cocultured with KK did not correlate with protein secretion. Downstream IGF signaling cascade components, phospho-Raf, phospho-MEK1/2, phospho-MAPK, PI-3 kinase, phospho-Akt, and phospho-Elk-1, were elevated in KF cocultured with KK. Addition of recombinant human IGFBP-3 or antibodies against IGF-I or IGF-IR significantly inhibited proliferation of KF. The bioavailability of IGF-I may be related to the levels of IGFBP-3 produced, which in turn influences KF proliferation, suggesting that modulation of IGF-I, IGF-IR, and IGFBP-3, individually or in combination, may represent novel approaches to the treatment of keloids.

scholarly journals Resection upregulates the IGF-I system of parenterally fed rats with jejunocolic anastomosis

2001 ◽  
Vol 281 (5) ◽  
pp. G1158-G1168 ◽  
Author(s):  
Melanie B. Gillingham ◽  
Karen R. Kritsch ◽  
Sangita G. Murali ◽  
Pauline Kay Lund ◽  
Denise M. Ney
Keyword(s):  
Parenteral Nutrition ◽  
Adaptive Growth ◽  
Differential Adaptation ◽  
Igf I ◽  
Igf Binding ◽  
Receptor Number ◽  
Igf Receptor ◽  
Igf Binding Protein ◽  
Igfbp 3

Rats maintained with parenteral nutrition following 60% jejunoileal resection plus cecectomy exhibit minimal adaptive growth in the residual jejunum but a dramatic adaptive growth in the residual colon. Coinfusion of insulin-like growth factor I (IGF-I) with parenteral nutrition induces jejunal growth but has minimal effects in the colon. Our objective was to study the role of the endogenous IGF-I system in the differential responses of jejunum and colon to resection and/or IGF-I during parenteral nutrition. We measured concentrations of immunoreactive IGF-I in plasma, jejunum, and colon, IGF-I receptor binding, and levels of IGF receptor, IGF-I, IGF binding protein (IGFBP)-3 and IGFBP-5 mRNA in residual jejunum and colon 7 days after resection and/or IGF-I treatment. IGF-I receptor number was increased (74–99%) in jejunum and colon due to resection; IGF-I mRNA was increased 5-fold in jejunum and 15-fold in colon due to resection. Resection increased circulating IGFBPs but did not alter plasma IGF-I concentration. Resection induced colonic growth in association with significantly greater colonic IGFBP-5 mRNA and significantly lower colonic immunoreactive IGF-I. IGF-I treatment had no significant effect on IGF-I mRNA or IGF-I receptor number. Concentrations of plasma and jejunal immunoreactive IGF-I were significantly increased in rats given IGF-I in association with jejunal growth. IGF-I treatment significantly increased IGFBP-5 mRNA in the jejunum, which also correlated with jejunal growth. Thus resection upregulated IGF-I receptor number and IGF-I mRNA in residual jejunum and colon, but differential adaptation of these segments correlated with differential regulation of IGFBP-5 mRNA.

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