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  • Articles: DFG German National Licenses  (5)
  • monocytes  (3)
  • Keywords Twins  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 17 (1979), S. 77-84 
    ISSN: 1432-0428
    Keywords: Insulin receptors ; insulin degradation ; glucose and lactate metabolism ; monocytes ; lymphocytes and mononuclear leucocytes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin binding, insulin degradation and glucose metabolism were studied in highly purified preparations of monocytes. Steady state specific insulin binding was found at 15 °C, whereas no plateau was reached at 37 °C because of considerable insulin degradation at this temperature.125I-insulin nonspecifically bound to monocytes at 15 °C remained constant for 120 min. In contrast non-specifically bound125I-insulin increased during incubation at 37 °C. About one third dissociated slowly to a washout medium suggesting an intracellular uptake of this fraction of non-specifically monocyte bound insulin. Monocytes did not degrade insulin at 15 °C. At 37 °C insulin was degraded partly by “proteases” released from the cells and partly by the specific insulin receptor. We found that about 35% of the total monocyte receptor bound iodoinsulin dissociated to a washout medium as degraded insulin. Furthermore, the degradation velocity of receptor bound insulin was proportional to the receptor occupancy. Thus, at 37 °C receptor bound insulin is the substrate for insulin degradation in monocytes and the reaction between the insulin molecule and the insulin receptor is conceivably considered not to be bimolecular at 37 °C unlike at 15 °C. Previously, no biological effect of insulin on monocytes has been demonstrated. In this study we found that insulin increased glucose uptake (25%, p〈0.01) and lactate release (12%, p〈0.05) in monocytes with ED50-values within the physiological range. To obtain 50% of maximal biological effect it was necessary to activate only a few percent of the receptors.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Twins ; non-insulin-dependent diabetes mellitus ; birth weight ; intrauterine malnutrition.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies have demonstrated an association between low weight at birth and risk of later development of non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this association is due to an impact of intrauterine malnutrition per se, or whether it is due to a coincidence between the putative “NIDDM susceptibility genotype” and a genetically determined low weight at birth. It is also unclear whether differences in gestational age, maternal height, birth order and/or sex could explain the association. Twins are born of the same mother and have similar gestational ages. Furthermore, monozygotic (MZ) twins have identical genotypes. Original midwife birth weight record determinations were traced in MZ and dizygotic (DZ) twins discordant for NIDDM. Birth weights were lower in the NIDDM twins (n = 2 × 14) compared with both their identical (MZ; n = 14) and non-identical (DZ; n = 14) non-diabetic co-twins, respectively (MZ: mean ± SEM 2634 ± 135 vs 2829 ± 131 g, p 〈 0.02; DZ: 2509 ± 135 vs 2854 ± 168 g, p 〈 0.02). Using a similar approach in 39 MZ and DZ twin pairs discordant for impaired glucose tolerance (IGT), no significantly lower birth weights were detected in the IGT twins compared with their normal glucose tolerant co-twins. However, when a larger group of twins with different glucose tolerance were considered, birth weights were lower in the twins with abnormal glucose tolerance (NIDDM + IGT; n = 106; 2622 ± 45 g) and IGT (n = 62: 2613 ± 55 g) compared with twins with normal glucose tolerance (n = 112: 2800 ± 51 g; p = 0.01 and p = 0.03, respectively). Furthermore, the twins with the lowest birth weights among the two co-twins had the highest plasma glucose concentrations 120 min after the 75-g oral glucose load (n = 86 pairs: 9.6 ± 0.6 vs 8.0 ± 0.4 mmol/l, p = 0.03). In conclusion, the association between low birth weight and NIDDM in twins is at least partly independent of genotype and may be due to intrauterine malnutrition. IGT was also associated with low birth weight in twins. However, the possibility cannot be excluded that the association between low birth weight and IGT could be due to a coincidence with a certain genotype causing both low birth weight and IGT in some subjects. [Diabetologia (1997) 40: 439–446]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Insulin receptors ; monocytes ; glucose tolerance ; insulin sensitivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied in normal man the inter-relationships between insulin binding to monocytes, glucose tolerance and insulin sensitivity. In 25 young healthy persons we found a significant positive correlation between insulin binding and glucose disappearance rate both after glucose (R = 0.68, p〈0.01) and insulin (R = 0.49, p〈0.02) given intravenously.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Twins ; Type-II (non-insulin-dependent) diabetes mellitus ; abnormal glucose tolerance ; concordance rates ; heritability.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To elucidate the relative importance of genetic and environmental factors on the development of Type II (non-insulin dependent) diabetes mellitus, we examined a sample of twins (n = 606) ascertained from the population-based Danish Twin Register. Based on a standard 75 g oral glucose tolerance test and current WHO criteria we identified 62 pairs in which one or both had Type II diabetes. The probandwise concordance (monozygotic: 0.50; dizygotic: 0.37) for Type II diabetes per se was not very different. When including the twins with impaired glucose tolerance (IGT), however, the probandwise concordance for abnormal glucose tolerance was significantly different between monozygotic (0.63) and dizygotic (0.43) twin pairs, (p 〈 0.01). These findings were supported by the heritability estimates for Type II diabetes per se (26 %) and for abnormal glucose tolerance (61 %). The metabolic variables, insulin resistance and insulin secretion, and anthropometric variables, body mass index and waist to hip ratio, known to be associated with the development of glucose intolerance had a heritability of 26, 50, 80 and 6 % respectively. This study confirms the notion of a multifactorial aetiology of Type II diabetes. It supports the contribution of non-genetic aetiological components in the development of Type II diabetes per se. The study also indicates a role for genes in the aetiology of abnormal glucose tolerance. We therefore propose that genetic predisposition is important for the development of abnormal glucose tolerance. Non-genetic factors, however, might play a predominant role in controlling whether a genetically predisposed individual progresses to overt Type II diabetes. [Diabetologia (1999) 42: 139–145]
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Insulin receptor ; monocytes ; thrombocytes ; negative cooperativity ; insulin degradation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have characterized the cellular composition of preparations isolated from peripheral blood by Ficoll-Isopaque gradient centrifugation.125I-insulin binding to every cell type was measured. A highly significantly positive correlation between specific cell binding fraction and the monocyte concentration of the heterogeneous cell suspension was demonstrated. Depletion of monocytes reduced the insulin binding approximately 80%, which confirms previous findings by other investigators. The granulocytes possessed the second highest binding ability, but only one fourteenth of that of monocytes. Compared to the lymphocyte the monocyte had about 25 times greater insulin binding. Also thrombocytes bound insulin and contamination with these meant that their contribution to the total specific cell binding was not negligible. A reduction in these contaminants is essential. We found that insulin binding to erythrocytes was insignificant. A method of calculating the specific insulin binding to monocytes alone is introduced. The monocyte-insulin-receptor possesses specificity. Only an insignificant degradation of receptor bound insulin could be shown. Evidence of negative cooperativity between receptors was found. Consequently monocytes are considered a useful model for insulin receptor studies in man.
    Type of Medium: Electronic Resource
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