Serum levels of insulin-like growth factors (IGF-I and IGF-II) and their binding protein (IGFBP-3) are not elevated in pancreatic cancer

1997 ◽  
Vol 22 (2) ◽  
pp. 95-100
Author(s):  
James D. Evans ◽  
Margaret C. Eggo ◽  
Ian A. Donovan ◽  
Simon R. Bramhall ◽  
John P. Neoptolemos
1995 ◽  
Vol 132 (4) ◽  
pp. 433-437 ◽  
Author(s):  
Burkhard Tönshoff ◽  
Werner F Blum ◽  
Mark Vickers ◽  
Sabine Kurilenko ◽  
Otto Mehls ◽  
...  

Tönshoff B, Blum WF, Vickers M, Kurilenko S, Mehls 0, Ritz E. Quantification of urinary insulin-like growth factors (IGFs) and IGF binding protein 3 in healthy volunteers before and after stimulation with recombinant human growth hormone. Eur J Endocrinol 1995;132:433–7. ISSN 0804–4643 We examined excretion of urinary insulin-like growth factors I and II (IGF-I and IGF-II) and their major binding protein IGFBP-3 in comparison to their respective serum concentration in nine healthy female volunteers (median age 25 years, range 22–27) under baseline conditions and after stimulation with recombinant human growth hormone (rhGH), 4.5 IU twice daily subcutaneously for a period of 3 days. The IGFs were measured in unconcentrated urine by use of recently developed, highly sensitive radioimmunoassays. The IGFBP-3 was measured by a specific radioimmunoassay. The mean (±sd) urinary concentrations of IGF-I (0.08 ± 0.07 μg/l), IGF-II (1.02 ± 0.47 μg/l) and IGFBP-3 (19.1 ± 6.9 μg/l) were two to three orders of magnitude lower than in serum. The ratio of IGF-II over IGF-I concentration in urine (13:1) was five times higher than in serum (2.5:1), and the ratio of IGFBP-3 over the sum of IGF-I and IGF-II in urine (17:1) was four times higher than in serum (4:1). Urinary excretion was 63.3 ± 46.6 ng·m−2 · 24 h−1 for IGF-I, 1002 ± 598 ng·m−2 · 24 h−1 for IGFII and 18039 ± 4983 ng·m−2·24 h−1 for IGFBP-3. Using fast protein liquid exclusion chromatography, only immunoreactive IGFBP-3 components of less than 60 kD were detected in urine, with a major peak at 20kD. Urinary IGFBP-3 excretion correlated with serum IGFBP-3 (r = 0.61, p < 0.01) and the glomerular filtration rate (r = 0.56, p < 0.05) measured by steady-state inulin infusion clearances. Administration of rhGH stimulated significantly (p < 0.005) the serum IGF-I concentration by 50%, but not the urinary IGF-I excretion. In conclusion: the considerably higher ratio of IGF-II to IGF-I in urine compared to serum indicates that urinary IGF excretion does not represent only filtered IGFs, urinary IGF-I is a less sensitive indicator of GH activity than serum IGF-I, and as urinary IGFBP-3 excretion is in proportion to the glomerular filtration rate and serum IGFBP-3, it presumably reflects renal filtration of small immunoreactive IGFBP-3 fragments from the circulation. Burkhard Tönshoff, University Children's Hospital, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany


1996 ◽  
Vol 150 (1) ◽  
pp. 121-127 ◽  
Author(s):  
C G Prosser ◽  
J Schwander

Abstract Plasma clearance of insulin-like growth factors-I and -II (IGF-I and -II) and insulin-like growth factor-binding protein-2 (IGFBP-2) from lactating goats (n=4) was determined following a single intravenous injection of the corresponding 125I-labelled human protein. Transfer of these proteins out of the vascular space was monitored by their subsequent appearance in mammary-derived lymph and milk. Clearance of 125I-IGFBP-2 from circulation was 0·37 ± 0·06 ml/min/kg, which is markedly greater than that of 125I-IGF-I or -II (0·11 ± and 0·12 ± 0·01 ml/min/kg respectively). This was also reflected in longer elimination half-lives for IGF-I (353 ± 6 min) and -II (254 ± 8 min) compared with IGFBP-2 (110 ± 9 min). Three hours after injection of the 125I-labelled protein, the plasma:lymph ratio of trichloroacetic acid-precipitable radioactivity was 1·54 ±0·04, 3·3 ±0·6 and 4·1 ±0·4 for IGFBP-2, IGF-I and -II respectively. The form of 125I-IGFBP-2 in lymph was not different from that of plasma. Elevation of plasma concentrations of IGFBP-2 by its intravenous infusion significantly decreased plasma half-life of both IGF-I and -II (251 ± 8 and 198 ±7 min respectively). Although the amount and rate of transfer of IGF into mammary-derived lymph was decreased slightly by IGFBP-2, concentrations eventually obtained were not different from control. However, secretion of IGFs into milk was significantly reduced by IGFBP-2, particularly in the case of IGF-I. These results are consistent with the ability of all three compounds to cross the vascular endothelium intact and of IGFBP-2 to decrease the uptake of IGF by mammary epithelium and subsequent secretion into milk. IGFBP-2 may well have acted to target plasma IGF towards non-mammary tissues, thus explaining the more rapid plasma clearance of IGFs in the presence of elevated IGFBP-2. Journal of Endocrinology (1996) 150, 121–127


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Somayeh Pouriamehr ◽  
Haleh Barmaki ◽  
Mozhdeh Rastegary ◽  
Farzaneh Lotfi ◽  
Mohsen Nabi Afjadi

Abstract Objective The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are thought to play a significant role in metabolic pathways and glucose metabolism. Unregulated levels of IGFs/IGFBPs have been associated with the development of glucose intolerance and metabolic syndrome X (MSx). We hypothesized that change of IGFs/IGFBPs levels could increase the risk of MSx; thus, this study aimed to evaluate the serostatus of IGFs/IGFBPs in individuals with MSx. Results After adjustment for metabolic parameters, MSx patients had a lower level of IGF-1, IGFBP-1, and IGFBP-2 compared with subjects in the control group. Further analysis revealed a positive correlation between serum levels of IGF-1 and IGF-2 (p < 0.05), as well as serum IGFBP-3 and IGF-2 (p < 0.05). Also, the statistical analysis showed a negative association of serum IGF-1 with plasma glucose and total cholesterol levels (p < 0.05). Besides, a negative relationship was found between serum concentrations of IGF-1/IGF-2 and the risk of developing MSx. These data indicated that some components of IGFs/IGFBPs are linked with the pathogenesis of MSx. In conclusion, these inverse associations showed a possible linkage between the IGF/IGFBP signaling pathway and the development of MSx. It seems the decreased concentrations of IGFs edmay be regarded as a potential biomarker for early diagnosis or even prognosis of MSx but need more systematic studies to confirmed it.


2011 ◽  
Vol 95 (8) ◽  
pp. 2753-2755 ◽  
Author(s):  
Angela F. Trinconi ◽  
José Roberto Filassi ◽  
José Maria Soares-Júnior ◽  
Edmund C. Baracat

2003 ◽  
Vol 4 (4) ◽  
pp. 213-224 ◽  
Author(s):  
Liam J. Murphy

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.


1994 ◽  
Vol 50 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Günter Rudolph ◽  
Werner F. Blum ◽  
Enno W. Jenne ◽  
Martin Schöning ◽  
Herbert Enders ◽  
...  

2020 ◽  
Author(s):  
Vanessa Y Tan ◽  
Caroline J Bull ◽  
Kalina M Biernacka ◽  
Alexander Teumer ◽  
Laura Corbin ◽  
...  

AbstractCirculating lipids have been associated with breast cancer (BCa). This association may, in part, be due to an effect of lipids on insulin-like growth factors (IGFs), which have been reliably associated with BCa. In two-sample Mendelian randomization (MR) analyses, we found that low density lipoprotein (LDL-C) was associated with IGFBP-3 (beta:0.08 SD; 95%CI:0.02,0.15; p = 0.01, per SD increase in LDL-C) and IGFBP-3 was associated with postmenopausal BCa (OR:1.09; 95%CI:1.00,1.19; p = 0.05, per SD increase in IGFBP-3). We also found that triglycerides were associated with IGF-I (beta:-0.13SD; 95%CI:-0.22,-0.03, per SD increase in triglycerides) and that IGF-I was associated with overall BCa (OR:1.10;95%CI:1.02,1.18, per SD increase in IGF-I). Taken together, these results suggest that IGFBP-3 may be a potential causal step between LDL-C and postmenopausal BCa and IGF-I a potential causal for triglycerides. Our two-step MR results build on evidence linking circulating lipids and IGFs with BCa, however, multivariable MR analyses are currently unable to support this relationship due to weak instruments.


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