scholarly journals Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus

2009 ◽  
Vol 28 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Milena Weber ◽  
Ivona Baričević-Jones ◽  
Romana Masnikosa ◽  
Dejan Filimonović ◽  
Željko Miković ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Binding Proteins ◽  
Gel Filtration ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Igf System ◽  
Igf I ◽  
Insulin Dependent ◽  
Insulin Like Growth Factors

Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus The IGF system of human placenta consists of insulin-like growth factors (IGF)-I and -II, their receptors (IGF-1R and IGF-2R), and binding proteins (IGFBP-1 to -6). Due to many structural and metabolic similarities with insulin, the IGF system cannot be examined separately from insulin and its receptor (IR). In this study gel filtration was used to detect solubilized membrane proteins of the placenta obtained from healthy mothers and mothers with IDDM. In order to detect placental membrane proteins that bind IGF molecules (and insulin), the solubilized membranes were incubated with each of the three 125I-labelled ligands: 125I-IGF-I, 125I-IGF-II and 125I-insulin prior to gel filtration chromatography. The biochemical evidence of the presence of receptors for insulin and IGFs, as well as that of IGFBP-1 were obtained by immunoblotting. Herein we demonstrated that, considering IGF and insulin receptor content, the placental tissue obtained from mothers with IDDM was not different from that obtained from healthy mothers. However, the concentration of IGFBP-1 differed between the examined placentas. IDDM in mothers caused an increase in the amount of IGFBP-1 in their placentas and, consequently, the amount of the labelled ligand bound to it. The redistribution of IGFs between the receptors and IGFBP-1 may be involved in regulatory mechanisms in the placenta of mothers with IDDM.

scholarly journals The effects of recombinant human IGF-I administration on concentrations of acid labile subunit, IGF binding protein-3, IGF-I, IGF-II and proteolysis of IGF binding protein-3 in adolescents with insulin-dependent diabetes mellitus

1998 ◽  
Vol 157 (1) ◽  
pp. 81-87 ◽  
Author(s):  
TD Cheetham ◽  
JM Holly ◽  
RC Baxter ◽  
K Meadows ◽  
J Jones ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Igf I ◽  
Igf Binding ◽  
Acid Labile Subunit ◽  
Insulin Dependent ◽  
Igf Binding Protein ◽  
Acid Labile ◽  
Igfbp 3

The long term therapeutic potential of recombinant human (rh) IGF-I administration in insulin-dependent diabetes mellitus (IDDM) may be determined by changes in the IGF binding proteins (IGFBPs) and thus the bioavailability of IGF-I. We have therefore studied the effects of a single subcutaneous dose of rhIGF-I (40 micrograms/kg at 1800 h), when compared with an untreated control night, in 17 subjects with IDDM, on serum concentrations of IGF-I, IGF-II, IGFBP-3, acid labile subunit (ALS), and IGFBP-3 proteolysis. Mean (+/- S.E.M.) IGF-I levels increased from 242 +/- 30 ng/ml to 399 +/- 26 ng/ml (P = 0.01) after rhIGF-I whereas IGF-II levels declined from 600 +/- 45 ng/ml to 533 +/- 30 ng/ml. There was a small overnight reduction in baseline ALS levels from 48 +/- 2.8 to 44.5 +/- 3.2 micrograms/ml (P = 0.04) after rhIGF-I administration. An early fall in IGFBP-3 concentrations on the control night was not seen after rhIGF-I and overall mean levels were increased (5.2 +/- 0.2 micrograms/ml vs 4.9 +/- 0.2 micrograms/ml, P = 0.04, on the control night). On the baseline night, IGFBP-3 levels correlated with the sum of IGF-I and IGF-II (r = 0.73, P = 0.02) and with levels of the ALS (r = 0.7, P = 0.002). However after rhIGF-I, the sum of IGF-I and IGF-II no longer correlated with IGFBP-3, whereas the relationship with ALS was maintained. Immunoblot studies in six subjects indicated that 60%-70% of the IGFBP-3 was detected as a low molecular weight fragment at 1900 h on both study nights, but the amount of fragment declined to approximately 50% at 0100 h and 45% at 0700 h. In conclusion, despite a slight but significant fall in ALS, IGFBP-3 levels rise after rhIGF-I administration in IDDM. This cannot be explained by alterations in IGFBP-3 proteolysis, and may relate to the relative stability of ALS/IGFBP-3 when complexed principally with IGF-I rather than IGF-II.

The effects of recombinant human insulin-like growth factor-I (IGF-I) administration on the levels of IGF-I, IGF-II and IGF-binding proteins in adolescents with insulin-dependent diabetes mellitus

1994 ◽  
Vol 142 (2) ◽  
pp. 367-374 ◽  
Author(s):  
T D Cheetham ◽  
A Taylor ◽  
J M P Holly ◽  
K Clayton ◽  
S Cwyfan-Hughes ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Igf Binding Proteins ◽  
Factor I ◽  
Igf I ◽  
Igf Binding ◽  
Insulin Dependent ◽  
Igfbp 3

Abstract Insulin-dependent diabetes mellitus (IDDM) during puberty is associated with a reduction in circulating concentrations of insulin-like growth factor-I (IGF-I) and low IGF bioactivity. Altered levels of the IGF-binding proteins (IGFBPs), including low IGFBP-3 and elevated IGFBP-1, have also been described. These abnormalities have been linked to poor growth and deteriorating blood glucose control. We have therefore examined the effects of recombinant human IGF-I (rhIGF-I) administration on the levels of IGF-I, IGF-II, IGFBP-1, IGFBP-3 and IGF bioactivity in a group of 9 late-pubertal adolescents with IDDM. This was a double-blind placebo controlled study with each individual admitted on two occasions when either rhIGF-I (40 μg/kg) or placebo was administered by subcutaneous injection in the thigh at 1800 h. Blood samples were then taken for the subsequent 22 h. The half-life of administered rhIGF-I (12·1–22·2 h) was similar to that previously described in normal subjects. There was a small increase in IGFBP-3 concentrations overnight following rhIGF-I administration when compared to placebo, whereas the levels of IGF-II decreased. Under strict euglycaemic conditions, the relationship between insulin and IGFBP-I did not appear to be affected by rhIGF-I administration although the levels of IGFBP-1 tended to be higher overnight. IGF bioactivity was low during the placebo study, and although within the normal adult range following administration of IGF-I, was still relatively low for adolescents in late puberty. Gel filtration chromatography revealed an increase in the fractions corresponding to the 150 kDa complex throughout the duration of the study and to a lesser extent the fractions corresponding to free IGF-I which reached a maximum of 7% of total IGF-I levels. In conclusion, the subcutaneous administration of rhIGF-I in a dose of 40 pg/kg to a group of adolescents with IDDM led to a sustained increase in IGF-I levels and a rise in IGF bioactivity despite a fall in IGF-II and a trend towards higher IGFBP-1 concentrations. Journal of Endocrinology (1994) 142, 367–374

scholarly journals Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1α Knockout Mouse

1998 ◽  
Vol 18 (5) ◽  
pp. 3059-3068 ◽  
Author(s):  
Ying-Hue Lee ◽  
Brian Sauer ◽  
Frank J. Gonzalez
Keyword(s):  
Diabetes Mellitus ◽  
Elevated Serum ◽  
Insulin Dependent Diabetes Mellitus ◽  
Regulatory Elements ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Null Mouse ◽  
Recombination System ◽  
Igf I ◽  
Insulin Dependent

ABSTRACT Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1α) were produced by use of the Cre-loxP recombination system. HNF-1α-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1α-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575–585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1α regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes.

Insulin-like growth factors and their binding proteins in pleural fluid

1997 ◽  
pp. 467-473 ◽  
Author(s):  
Y Le Bouc ◽  
A Bellocq ◽  
C Philippe ◽  
L Perin ◽  
M Garabedian ◽  
...  
Keyword(s):  
Growth Factors ◽  
Pleural Fluid ◽  
Binding Proteins ◽  
Specific Binding ◽  
Gel Filtration ◽  
Specific Protein ◽  
Hydroxyvitamin D ◽  
Igf I ◽  
Acid Gel ◽  
Insulin Like Growth Factors

We investigated the expression and potential regulatory role of insulin-like growth factors (IGFs) and their specific binding proteins (BPs) in tuberculous and nontuberculous pleuritis. By using a radioimmunoassay after acid gel filtration chromatography, we found that mean concentrations of IGF-I were 211.9 +/- 20.2 microg/l and 203.2 +/- 31.1 microg/l in pleural fluid of 14 patients with tuberculous pleuritis and 9 patients with malignant pleuritis respectively. These values were near those in serum of the same patients (221.3 +/- 19.5 microg/l and 204.6 +/- 21.0 microg/l respectively). By using a specific protein-binding assay, we found that mean concentrations of IGF-II were 345.3 +/- 61.0 microg/l and 167.6 +/- 22.7 microg/l in tuberculous and malignant pleural effusions respectively. These values were significantly lower than those in serum of the same patients (628.3 +/- 79.0 microg/l, P<0.025 and 532.0 +/- 85.9 microg/l, P<0.025 respectively). Because bioavailability and bioactivity of IGFs may be regulated by their binding to IGFBPs, we studied IGFBP patterns in the pleural fluid of 6 patients with tuberculous pleuritis. As assessed by Western ligand blotting the levels of IGFBP-1 and IGFBP-2 were increased whereas those of IGFBP-3 were decreased in pleural fluid in comparison with serum. The decrease in IGFPB-3 levels reflected increased proteolysis, as assessed by Western immunoblotting. In spite of this presence of IGFBPs, IGFs could be responsible for the local biosynthesis of 1.25-dihydroxyvitamin D (1,25-(OH)2D) since pleural fluid levels of both IGF-I and IGF-II significantly correlated with those of 1,25-(OH)2D. These results indicate that IGFs are detectable in pleural fluid and may contribute to control the activity of 25-hydroxyvitamin D-1alpha hydroxylase in tuberculous pleuritis.

Insulin-like growth factor binding proteins in prepubertal children with insulin-dependent diabetes mellitus

1995 ◽  
Vol 133 (4) ◽  
pp. 440-444 ◽  
Author(s):  
Mikael Knip ◽  
Päivi Tapanainen ◽  
Fredrika Pekonen ◽  
Werner F Blum
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Like Growth Factor ◽  
Prepubertal Children ◽  
Igf I ◽  
Diabetic Children ◽  
Insulin Dependent

Knip M, Tapanainen P, Pekonen F, Blum WF. Insulin-like growth factor binding proteins in prepubertal children with insulin-dependent diabetes mellitus. Eur J Endocrinol 1995:133:440–4. ISSN 0804–4643 To study the possible role of insulin-like growth factor binding proteins (IGFBPs) in the discrepancy between normal or only slightly retarded growth and substantially reduced concentrations of insulin-like growth factor I (IGF-I) in prepubertal children with insulin-dependent diabetes mellitus (IDDM), we measured the plasma concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 and free insulin in 24 prepubertal diabetic subjects and 12 control children. In addition, the growth hormone response to exercise was evaluated. The diabetic children had significantly decreased peripheral IGF-I levels (8.2 + 1.1 (sem) vs 16.7 + 2.5 nmol/l; p < 0.001), whereas the concentrations of free insulin were increased (217 + 14 vs 103 + 21 pmol/l; p < 0.001). The concentrations of IGFBP-1 and IGFBP-3 were of the same magnitude in both groups. The diabetic children had significantly increased levels of IGFBP-2 (465 + 13 vs 416 + 14 μg/l; p = 0.029), which were inversely related to the circulating IGF-I levels (r = −0.35; p = 0.034). The diabetic and control children had comparable growth hormone responses to exercise. Diabetic children with poor glucose control had even lower IGF-I levels than those with moderate metabolic control (6.0 + 0.8 vs 10.3 + 1.7 nmol/l; p = 0.037). No differences could be observed in the plasma concentrations of various IGFBPs between these two groups of diabetic subjects. The absence in prepubertal diabetic children of increased IGFBP-1 levels observed in adolescent and adult patients with IDDM may contribute to their maintained linear growth, despite definitely decreased IGF-I concentrations. The role of increased IGFBP-2 levels in prepubertal children with IDDM remains open, but the inverse relationship between IGF-I levels and IGFBP-2 concentrations suggests that IGF-I may be involved in the regulation of IGFBP-2. Mikael Knip, Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland

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