Home About us Contact
|
Home About us Contact | ||
|
|
||
IGF-binding Proteins (IGF-bind + protein)
Selected AbstractsProfound changes in the GH,IGF-I system in adolescent girls with IDDM: can IGFBP1 be used to reflect overall glucose regulation?PEDIATRIC DIABETES, Issue 3 2000MU Halldin Disturbances in the relations between insulin, growth hormone (GH) and insulin-like growth factor I (IGF-I) may be a major cause behind deteriorated metabolic control in adolescent girls with type I diabetes. These patients have increased GH secretion and low IGF-I concentrations. The aim of this study was to identify possible endocrine mechanisms behind good and poor glycaemic control in such girls, focusing on the insulin,GH,IGF-I axis. Ten girls with well-controlled insulin-dependent diabetes mellitus (IDDM), hemoglobin A1c (HbA1c) 6.5±0.4% (normal range 3.9,5.2%) and nine healthy controls were investigated and compared with 11 girls with poor glucose regulation, HbA1c 10.9±0.4%, and their corresponding controls. Serum profiles of glucose, insulin, GH and IGF-binding protein 1 (IGFBP1) were analysed in addition to IGF-I and HbA1c. Two interesting observations were made. GH concentrations were equally elevated in the two diabetic groups regardless of metabolic control (mean 24 h GH , girls with poorly controlled diabetes 10.0±1.0 mU/L vs 9.8±1.7 , girls with well-controlled diabetes; p=ns). Likewise, the IGF-I concentrations were reduced to the same extent (233±19 vs 242±23 ,g/L; p=0.75). Secondly, despite similar insulin concentrations (mean 24 h insulin , girls with poorly controlled diabetes 22.9±2.6 and girls with well-controlled diabetes 27.3±2.9 mU/L, respectively; p=0.26), there was a marked difference in IGFBP1 concentrations between the two groups with IDDM (mean IGFBP1 , girls with poorly controlled diabetes 70.5±9.1 ,g/L vs girls with well-controlled diabetes 28.6±3.3; p<0.001). Despite equally elevated GH concentrations that may induce insulin resistance, the markedly lower concentrations of IGFBP1 in the well-controlled group indicate a higher hepatic insulin sensitivity in these girls compared with those with a poor control. Furthermore, in spite of similar total IGF-I concentrations, the lower IGFBP1 concentrations may result in higher IGF-I bioactivity in the well-controlled group. This may be reflected in better growth of the well-controlled group whose height of 168.7±0.9 vs 163.6±1.2 cm was significantly different (p<0.004). IGFBP1 may be a marker of overall insulinization in adolescents with type 1 diabetes, independent of the absolute insulin dose used for therapy. [source] Insulin-like Growth Factor (IGF)-I, IGF-binding Protein-3 and Colorectal Adenomas in Japanese MenCANCER SCIENCE, Issue 11 2002Satoshi Teramukai Several epidemiological studies have found that high levels of plasma insulin-like growth factor (IGF)-I and low levels of IGF-binding protein (IGFBP)-3 are related to an increased risk of colorectal cancer or late-stage adenomas. We examined the relation of body mass index, fasting and 2-h postload plasma glucose levels and plasma concentrations of IGF-I and IGFBP-3 to colorectal adenomas in middle-aged Japanese men. The study subjects comprised 157 cases of histologically diagnosed colorectal adenomas and 311 controls with normal colonoscopy or non-polyp benign lesions in a consecutive series of 803 men receiving a preretirement health examination at two hospitals of the Self Defense Forces (SDF). After adjustment for rank in the SDF, hospital, smoking and IGFBP-3, a statistically nonsignificant modest increase in the prevalence odds of colorectal adenomas was observed for the highest versus the lowest quartile level of IGF-I. The increase was slightly greater with further adjustment for 2-h glucose concentrations (adjusted odds ratio 1.8, 95% confidence interval 1.0,4.5, trend P=0.06). Men with high levels of IGFBP-3 showed only a minimal decrease in risk after adjustment for IGF-I. The association with IGF-I was less evident for advanced adenomas (,5 mm in size or tubulovillous/villous). Fasting and 2-h glucose and body mass index were more strongly positively associated with colorectal adenomas than IGF-I, especially with advanced adenomas, independently of IGF-I and IGFBP-3. The findings suggest that plasma IGF-I and IGFBP-3 may be involved in colorectal tumorigenesis regardless of the stage in growth of adenoma, but not as a mediator for the effects of being overweight or of hyperglycemia. [source] The role of IGF-I and its binding proteins in the development of type 2 diabetes and cardiovascular diseaseDIABETES OBESITY & METABOLISM, Issue 3 2008Vivienne A. Ezzat Patients with insulin resistance and type 2 diabetes have an excessive risk of cardiovascular disease (CVD); this increased risk is not fully explained by traditional risk factors such as hypertension and dyslipidaemias. There is now compelling evidence to suggest that abnormalities of insulin-like growth factor-I (IGF-I) and one of its binding proteins, insulin-like growth factor-binding protein-1 (IGFBP-1), occur in insulin-resistant states and may be significant factors in the pathophysiology of CVD. We reviewed articles and relevant bibliographies following a systematic search of MEDLINE for English language articles between 1966 and the present, using an initial search strategy combining the MeSH terms: IGF, diabetes and CVD. Our aim was first to review the role of IGF-I in vascular homeostasis and to explore the mechanisms by which it may exert its effects. We also present an overview of the physiology of the IGF-binding proteins, and finally, we sought to summarize the evidence to date describing the changes in the insulin/IGF-I/IGFBP-1 axis that occur in type 2 diabetes and CVD; in particular, we have focused on the potential vasculoprotective effects of both IGF-I and IGFBP-1. We conclude that this system represents an interesting and novel therapeutic target in the prevention of CVD in type 2 diabetes. [source] Role of the IGF-II receptor in mediating acute, non-genomic effects of retinoids and IGF-II on keratinocyte cell deathEXPERIMENTAL DERMATOLOGY, Issue 4 2003F. Louafi Abstract:, In this study, we have examined the effects of retinoic acid (RA) on the human immortalized keratinocyte cell line (HaCaT). A significant twofold (P < 0.01) increase in apoptotic cell death compared with the control was found within 24 h of treatment with 10,5 M of RA. Apoptosis was confirmed by flow cytometry. Cycloheximide did not inhibit this acute RA-induced apoptosis. Interestingly, insulin-like growth factor-II (IGF-II, 50 ng/ml) was able to significantly (67.3%; P < 0.05) reduce RA effects, whereas IGF-I (50 ng/ml) and insulin (75 ng/ml) were without effect. Furthermore, analogues of IGF-II [leu27 IGF-II and Des(1-6) IGF-II], with altered affinities for the IGF-I receptor and IGF-binding proteins (IGFBPs), but retained affinities for the IGF-II receptor, also completely inhibited (100%; P < 0.01) RA-induced apoptosis, while an IGF-I receptor antagonist did not reduce the survival effects of IGF-II. Insulin pretreatment negates the survival effect of IGF-II. In contrast, mannose 6 phosphate (M6P) did not alter RA or IGF-II actions. These results indicate that rapid induction of cell death by RA is independent of production or secretion of new proteins. The inhibition of RA action by IGF-II was independent of its ability to signal through the IGF-I receptor or to interact with IGFBPs. [source] Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer,INTERNATIONAL JOURNAL OF CANCER, Issue 2 2004Annekatrin Lukanova Abstract Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91,11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65,11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15,0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22,1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer. © 2003 Wiley-Liss, Inc. [source] Insulin-like growth factors in patients with liver cystsJOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2004Olgica Nedi Abstract Insulin-like growth factors (IGFs) play an important role in cell growth and differentiation, and the liver is the main source of IGFs and IGF-binding proteins (IGFBPs) that appear in the circulation. The effect of liver cysts on the circulating IGF system was studied in this work. Serum concentrations of IGF-I and -II were measured by radioimmunoassay, IGFBP patterns were characterised by ligand-affinity and immunoblotting, and a lectin-binding assay was used to investigate the glyco component of IGFBP-3 complexes. IGF-I and -II concentrations in patients with cysts were significantly lower compared to those in healthy individuals (P<0.0001 and P<0.01, respectively), and the decrease was related to age but not sex. The overall mean concentrations of IGF-I and -II were not significantly different whether the cysts were caused by Echinococcus granulosus, cross-reactive pathologies, or some other factor. IGFBP profiles correlated with the amount of IGF present: patients with lower IGF-I concentrations expressed decreased IGFBP-3 and elevated IGFBP-2 levels. Increased IGFBP-3 proteolytic activity in the patients' blood was not detected by immunoblotting. In the lectin-binding assay, IGFBP-3 complexes in the circulation of patients demonstrated reactivity similar to that in healthy persons, suggesting that the overall structure of the saccharide moieties of the IGFBP-3 complexes was not significantly altered due to liver cyst formation. J. Clin. Lab. Anal. 18:299,304, 2004. © 2004 Wiley-Liss, Inc. [source] Weight control and physical activity in cancer preventionOBESITY REVIEWS, Issue 1 2002Franca Bianchini Summary Overweight and obesity have reached epidemic dimensions worldwide, mainly due to consumption of high energy diets and increased sedentary behaviour. Overweight and insufficient physical activity are clearly associated with cardiovascular diseases and type 2 diabetes. Evidence is also accumulating that they may also increase cancer risk, particularly in the colon, breast and endometrium. This effect seems to be mediated by alterations in the metabolism of endogenous hormones, including sex steroids and insulin, and levels of insulin-like growth factor(IGF)-I and IGF-binding proteins. In light of the beneficial effects of weight control and physical activity for cancer prevention, a healthy lifestyle, keeping a low body weight and exercising most days of the week, is recommended. [source] Involvement of ligand occupancy in Insulin-like growth factor-I (IGF-I) induced cell growth in osteoblast like MC3T3-E1 cellsBIOFACTORS, Issue 4 2007Seok-Kwun Kim Abstract Growth factors and matrix proteins regulate the proliferation and differentiation of osteoblasts. The insulin-like growth factor (IGF) system comprises IGF-I, IGF-II, and six high-affinity IGF-binding proteins (IGFBPs). IGFs stimulate cell growth in many types of tissue; IGF-binding proteins regulate cellular actions and can affect cell growth. IGF-I is involved in differentiation, proliferation, and matrix formation in osteoblasts; IGFBP-5 is associated with the extracellular matrix (ECM) and can potentiate the actions of IGF-I. We investigated the effect of ECM proteins on the responses of MC3T3-E1 osteoblast cells to IGF-I and IGFBP-5. In addition, because extracellular signal-regulated kinases 1 and 2 (Erk 1/2) affect cell growth, we evaluated the effects of IGFBP-5 on Erk 1/2 phosphorylation in MC3T3-E1 cells. IGF-I caused an increase in IGFBP-5 expression in cultured MC3T3-E1 cells, and IGF-I plus IGFBP-5 significantly increased cell growth. Likewise, the addition of IGF-I and IGFBP-5 to cultured MC3T3-E1 cells increased the synthesis of the ECM proteins osteopontin (OPN) and thrombospondin-1 (TSP-1), which can bind to ,V,3 integrin receptors on the cell surface. By contrast, the addition of an antibody against ECM proteins inhibited the effects of OPN and TSP-1 on IGFBP-5 expression. The stimulatory effect of IGFBP-5 was mediated via Erk 1/2 activation. These data suggest that IGFBP-5 regulates Erk 1/2 phosphorylation in cultured MC3T3-E1 cells via ECM proteins that may ultimately stimulate the growth of osteoblasts. We determined whether occupation of the ,V,3 integrin receptor affects IGF-I receptor (IGF-IR)-mediated signaling and function in MC3T3-E1 osteoblast cells. Occupation of the ,V,3 integrin receptor with ECM proteins induced IGF-I-stimulated IGF-IR phosphorylation. Conversely, in the presence of the ,V,3-specific disintegrin echistatin, IGF-I-stimulated IGF-IR activation was inhibited. IGF-I-stimulated IGF-IR phosphorylation was accompanied by IRS-1 phosphorylation and MAPK activation. However, these effects were attenuated by echistatin. Thus, occupancy of the ,V,3 disintegrin receptor modulates IGF-I-induced IGF-IR activation and IGF-IR-mediated function in MC 3T3-E1 osteoblasts. [source] | |||||||||||||||||||