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  • 1
    Electronic Resource
    Electronic Resource
    Binding and biological effects of insulin, insulin analogues and insulin-like growth factors in rat aortic smooth muscle cells. Comparison of maximal growth promoting activities (1991)
    Springer
    Diabetologia 34 (1991), S. 307-313 
    Details
    ISSN: 1432-0428
    Keywords: Insulin ; insulin analogues ; insulin-like growth factors ; proliferation ; vascular smooth muscle cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Binding and growth promoting effects of insulin, insulin analogues modified in the B chain, proinsulin, insulin-like growth factor-I and -II were studied in cultured rat aortic smooth muscle cells. Specific binding of125I-insulin was 0.9±0.2% of total 125I-insulin added, and the IC50-value was estimated to 8.9 pmol/1. The insulin analogue B10 Asp tended to be more potent than insulin in displacing 125I-insulin, B28 Asp was equipotent, B9 Asp/B27 Glu was approximately 100 times less potent and insulin-like growth factor-I more than 1000 times less potent than insulin. Specific binding of 125I-insulin-like growth factor-I after 4 h incubation at 10 °C was five times higher than the specific binding of insulin (4.4±0.4% of total 125I-insulin-like growth factor-I added), and the IC50-value was 0.3 nmol/l. Insulin was approximately 500 times less potent than insulin-like growth factor-I in displacing 125I-insulin-like growth factor-I. The insulin analogue B10 Asp was slightly more potent and analogue B28 Asp was equipotent with insulin. Analogue B9 Asp/B27 Glu was ten times less potent and proinsulin was more than ten times less potent than insulin. The order of potency was similar for 3H-thymidine incorporation into DNA: insulin-like growth factor-I 〉 B10 Asp 〉 insulin-like growth factor-II 〉 insulin 〉 B28 Asp 〉 B9 Asp/B27 Glu 〉 proinsulin. The maximal effect of insulin-like growth factor-I on 3H-thymidine incorporation was 71±16% higher than the maximal effect of insulin. The maximal effect of insulin-like growth factor-II was at least as high as the effect of insulin-like growth factor-I. Furthermore, the maximal effect of B10 Asp was 62±10% higher than the maximal effect of insulin. Insulin-like growth factor-I and B10 Asp tended to increase cell number more than insulin. In conclusion, this study shows that insulin analogues interact with different potencies with receptors for insulin and insulin-like growth factor-I in vascular smooth muscle cells and that insulin-like growth factors and the insulin analogue B10 Asp have more pronounced growth effects than insulin. Substitution of the amino acid Asp for His at position B10 in insulin makes the molecule more similar to insulin-like growth factor-I, chemically and probably also biologically.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00405001
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Somatomedin C in the pancreas of young and adult, normal and obese, hyperinsulinemic mice (1989)
    Springer
    Cell & tissue research 255 (1989), S. 467-474 
    Details
    ISSN: 1432-0878
    Keywords: Insulin-like growth factor I ; Somatomedin C ; Hyperinsulinemia ; Liver ; Pancreas, endocrine ; Endocrine cells ; D cells ; Mice, hyperinsulinemic: obese (ob/ob), lean (l/l) ; Mouse l/l
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Immunocytochemical, immunochemical and RNA-hybridization techniques were used to map the distribution of somatomedin C (Sm-C; insulin-like growth factor I; IGF-I) in the pancreas of young and adult lean and obese mice. The D cells in the islets of Langerhans showed intense cytoplasmic Sm-C immunoreactivity, extending into their processes. Only slight Sm-C immunoreactivity was seen in A and B cells, apparently confined to the plasma membranes. In the exocrine pancreas scattered duct cells were immunopositive. Starvation increased, while feeding decreased the Sm-C immunoreactivity in B cells. RNA-hybridization analyses revealed that roughly the same number of Sm-C mRNA molecules, as calculated per DNA amount in the pancreas, could be demonstrated in young and adult, lean and obese mice. Radioimmunoassay (RIA) determinations of total Sm-C showed that there were about equal concentrations in the pancreas of lean and obese mice. There were marked differences between the liver and the pancreas, in that the RIA Sm-C values for the former were twice those in the latter while, in contrast, the corresponding values for the Sm-C mRNA, i.e. the agent determining the synthesis of Sm-C, were about 100 times higher in the liver as compared to that in the pancreas. We interpret our results as follows: The D cells in the islets form and secrete Sm-C in both young and adult, lean and obese mice, while A and B cells bind, but do not necessarily synthesize this peptide. Our results obtained in vivo on mature pancreatic tissue are in contrast to those obtained in tissue-culture studies on fetal and neonatal islets, in which B cells synthesize Sm-C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00224132
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    Paper (German National Licenses)
    Fulltext
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