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  • 1
    Electronic Resource
    Electronic Resource
    Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension (1996)
    Springer
    Diabetologia 39 (1996), S. 952-960 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor ; IGF-I receptor ; hybrid receptor ; insulin resistance ; gestational hypertension ; placenta
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gestational hypertension is associated with insulin-resistance; insulin and insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role in the growth of the feto-placental unit. Since both receptors are exposed to the maternal circulation, it has been suggested that maternal metabolic abnormalities might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify this issue, we characterized HIR and IGF-1R in placenta at term from normal women, normoinsulinaemic women with gestational hypertension (NGH), and hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was decreased in HGH women (B/T 0.12±0.03) compared to control and NGH women (B/T 0.18±0.07, p〈0.036; and 0.22±0.5, p〈0.009 respectively). Receptor affinity was lower in HGH women (ED50 0.95±0.32 nmol/l) than control and NGH women (ED50 0.42±0.19 nmol/l, p〈0.01; and 0.40±0.1 nmol/l, p〈0.007, respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+ 50±7,%) than in control and NGH women (Ex11+ 34±9%, p〈0.001; and 39±4%, p〈0.01, respectively). Increased expression of Ex11+ isoform was correlated with ED50 (r=0.71; p〈0.002) and insulinaemia (r=0.70, p〈0.002). IGF-I binding was increased in HGH women (B/T 0.17±0.03) compared to control and NGH women (B/T 0.09±0.05, p〈0.002; and 0.11±0.03, p〈0.002, respectively). IGF-IR affinity was similar in the three groups. The percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85±3%) compared to control and NGH women (68±7%, p〈0.001; and 63±9%, p〈0.001, respectively), and was positively correlated with insulinaemia (r=0.62, p〈0.018), ED50 of insulin binding (r=0.62, p〈0.05), and maximal IGF-I binding (r=0.69, p〈0.004); whereas it was inversely correlated with maximal insulin binding (r=−0.69, p〈0.004). Results provide the first evidence for altered expression of insulin/IGF-I hybrids found in insulin-resistance states.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403915
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 2
    Electronic Resource
    Electronic Resource
    Delayed intracellular dissociation of the insulin-receptor complex impairs receptor recycling and insulin processing in cultured Epstein-Barr virus-transformed lymphocytes from insulin-resistant subjects (1996)
    Springer
    Diabetologia 39 (1996), S. 289-297 
    Details
    ISSN: 1432-0428
    Keywords: Insulin receptor ; receptor internalization ; insulin resistance ; glucose toxicity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-receptor internalization and processing are defective in insulin-resistant subjects. To assess the reversibility of these defects, we cultured Epstein-Barr virus-transformed-lymphoblasts from six normal, six obese, and six non-insulin-dependent diabetic (NIDDM) subjects in media containing low (5 mmol/l) or high (25 mmol/l) glucose concentrations, and studied the insulin-receptor internalization and processing in vitro. In cells from normal, obese, and NIDDM subjects cultured in low glucose concentrations, exposure to 100 nmol/l insulin for 30 min at 37
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418344
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Increased expression of low-affinity insulin receptor isoform and insulin/insulin-like growth factor-I hybrid receptors in term placenta from insulin-resistant women with gestational hypertension (1996)
    Springer
    Diabetologia 39 (1996), S. 952-960 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor ; IGF-I receptor ; hybrid receptor ; insulin resistance ; gestational hypertension ; placenta.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Gestational hypertension is associated with insulin-resistance; insulin and insulin-like growth factor-1 (IGF-1), acting through their receptors, play a role in the growth of the feto-placental unit. Since both receptors are exposed to the maternal circulation, it has been suggested that maternal metabolic abnormalities might affect placental insulin (HIR) and IGF-1 (IGF-1R) receptors. To clarify this issue, we characterized HIR and IGF-1R in placenta at term from normal women, normoinsulinaemic women with gestational hypertension (NGH), and hyperinsulinaemic women with gestational hypertension (HGH). Insulin binding was decreased in HGH women (B/T 0.12 ± 0.03) compared to control and NGH women (B/T 0.18 ± 0.07, p 〈 0.036; and 0.22 ± 0.5, p 〈 0.009 respectively). Receptor affinity was lower in HGH women (ED50 0.95 ± 0.32 nmol/l) than control and NGH women (ED50 0.42 ± 0.19 nmol/l, p 〈 0.01; and 0.40 ± 0.1 nmol/l, p 〈 0.007, respectively), whereas low-affinity Ex11+ isoform was higher in HGH women (Ex11+ 50 ± 7, %) than in control and NGH women (Ex11+ 34 ± 9 %, p 〈 0.001; and 39 ± 4 %, p 〈 0.01, respectively). Increased expression of Ex11+ isoform was correlated with ED50 (r = 0.71; p 〈 0.002) and insulinaemia (r = 0.70, p 〈 0.002). IGF-I binding was increased in HGH women (B/T 0.17 ± 0.03) compared to control and NGH women (B/T 0.09 ± 0.05, p 〈 0.002; and 0.11 ± 0.03, p 〈 0.002, respectively). IGF-IR affinity was similar in the three groups. The percentage of insulin/IGF-I hybrid receptors was increased in HGH women (85 ± 3 %) compared to control and NGH women (68 ± 7 %, p 〈 0.001; and 63 ± 9 %, p 〈 0.001, respectively), and was positively correlated with insulinaemia (r = 0.62, p 〈 0.018), ED50 of insulin binding (r = 0.62, p 〈 0.05), and maximal IGF-I binding (r = 0.69, p 〈 0.004); whereas it was inversely correlated with maximal insulin binding (r = −0.69, p 〈 0.004). Results provide the first evidence for altered expression of insulin/IGF-I hybrids found in insulin-resistance states. [Diabetologia (1996) 39: 952–960]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00403915
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Delayed intracellular dissociation of the insulin-receptor complex impairs receptor recycling and insulin processing in cultured Epstein-Barr virus-transformed lymphocytes from insulin-resistant subjects (1996)
    Springer
    Diabetologia 39 (1996), S. 289-297 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin receptor ; receptor internalization ; insulin resistance ; glucose toxicity.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin-receptor internalization and processing are defective in insulin-resistant subjects. To assess the reversibility of these defects, we cultured Epstein-Barr virus-transformed-lymphoblasts from six normal, six obese, and six non-insulin-dependent diabetic (NIDDM) subjects in media containing low (5 mmol/l) or high (25 mmol/l) glucose concentrations, and studied the insulin-receptor internalization and processing in vitro. In cells from normal, obese, and NIDDM subjects cultured in low glucose concentrations, exposure to 100 nmol/l insulin for 30 min at 37 °C reduced cell-surface 125I-insulin binding to a similar extent (82 ± 2, 77 ± 5, and 82 ± 5 % of initial values, respectively). The same results were obtained with cells cultured in high glucose concentrations. In cells cultured under both glucose conditions, and exposed to 100 nmol/l insulin for 30 min at 37 °C, a complete recovery of the initial 125I-insulin binding was observed in normal but not in obese and NIDDM subjects. Release of intracellular insulin and its degradation in vitro was determined by incubating cells with 600 pmol/l of 125I-insulin for 60 min at 37 °C, acid washing cells, and re-incubating in insulin-free buffer at 37 °C. The radioactivity released by cells was characterized by trichloroacetic acid precipitability, Sephadex G-50 column chromatography, and re-binding to fresh cells. Rates of release of internalized radioactivity were reduced in obese and NIDDM subjects (t1/2 = 61 ± 9 min, p 〈 0.02; 58 ± 10 min, p 〈 0.05; and 38 ± 4 min in obese, NIDDM, and normal subjects, respectively). The percentage of intact insulin released from cells was significantly higher in obese and NIDDM subjects than in the normal subjects. The t1/2 of intracellular dissociation of insulin-receptor complexes measured by a polyethylene glycol assay was lower in normal (6 ± 1 min) than in obese (12 ± 2 min, p 〈 0.03) and NIDDM subjects (14 ± 3 min, p 〈 0.02). The results suggest that in insulin-resistant subjects a primary defect in intracellular dissociation of insulin is responsible for alterations of receptor recycling and insulin processing. [Diabetologia (1996) 39: 289–297]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418344
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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