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  • 1
    ISSN: 1432-0428
    Schlagwort(e): Proinsulin ; split proinsulin ; immunoradiometric assay ; Type 2 (non-insulin-dependent) diabetes mellitus ; impaired Beta-cell function
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Plasma insulin, intact proinsulin and 32–33 split proinsulin measured by specific immunoradiometric assays and insulin and C-peptide measured by radioimmunoassay were measured during a constant infusion of glucose test in ten diet-treated subjects with a history of Type 2 (non-insulin-dependent) diabetes (termed diabetic subjects), mean fasting plasma glucose 6.0 ± 1.0 mmol/l (mean ± SD), and 12 non-diabetic control subjects. Immunoreactive insulin concentrations measured by radioimmunoassay were 33 higher than insulin and 16 % higher than the sum of insulin and its precursors by immunoradiometric assay. The diabetic and non-diabetic subjects had similar fasting concentrations of insulin, intact proinsulin and 32–33 split proinsulin. The ratio of fasting intact proinsulin to total insulin was greater in the diabetic than the non-diabetic group 12.0 % (6.8–21.0 %, 1 SD range) and 6.3 % (4.0–9.8 %), respectively,p 〈 0.01), though the groups overlapped substantially. After glucose infusion, diabetic and non-diabetic subjects had similar intact proinsulin concentrations (geometric mean 4.9 and 5.2 pmol/l, respectively), but the diabetic group had impaired insulin secretion by immunoradiometric assay (geometric means 55 and 101 pmol/1,p 〈 0.05) or by radioimmunoassay C-peptide (geometric means 935 and 1410 pmol/1,p 〈 0.05), though not by radioimmunoassay insulin (87 and 144 pmol/1,p = 0.12), respectively. Individual immunoradiometric assay insulin responses to glucose expressed in terms of obesity were subnormal in nine of ten diabetic subjects. Radioimmunoassay insulin and C-peptide gave less complete discrimination ( subnormal responses in six of ten and eight of ten, respectively). Thus, raised proinsulin and proinsulin:total insulin ratio are not necessarily a feature of mild diet-treated Type 2 diabetic patients with subnormal insulin responses to glucose.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-0428
    Schlagwort(e): 32–33 splet-proinsulin ; Total cholesterol ; high density lipoprotein cholisterol ; plasminogen activator inhibitor ; Blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Standard radioimmunoassay for insulin may substantially overestimate levels of insulin because of cross-reaction with other insulin-like molecules. We have measured concentrations of insulin, intact proinsulin and 32–33 split proinsulin using two-site monoclonal antibody based immunoradiometric assays, and of insulin by a standard radioimmunoassay (“immunoreactive insulin”) in 51 Type 2 (noninsulin-dependent) diabetic subjects in the fasting state. The relationships of these concentrations were sought with those of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglyceride, plasminogen activator inhibitor, blood pressure, and indices of body fat distribution. Significant relationships were apparent between concentrations of “immunoreactive insulin” as measured by standard radioimmunoassay and triglyceride (r s=0.42, p〈0.001), total cholesterol (r s=0.25, p=0.038), high density lipoprotein cholesterol (r s=−0.30, p=0.018) and body mass index (r s=0.30, p=0.017), but only the relationships with triglyceride (r s=0.36, p=0.006) and body mass index (r s=0.26, p=0.034) remained significant when concentrations of immunoradiometrically measured insulin were employed. Concentrations of 32—33 split proinsulin, which comprises the major insulin-like molecule in these subjects, correlated positively with triglyceride (r s=0.33, p=0.009), total cholesterol (r s=0.23, p=0.050), and plasminogen activator inhibitor (r s=0.26, p=0.049), and negatively with high density lipoprotein cholesterol (r s=−0.29, p=0.021). Concentrations of “immunoreactive insulin” and immunoradiometric assay insulin showed significant positive correlaion with both systolic (r s=0.24, p=0.044 and r s=0.29, p=0.020 respectively), and diastolic blood pressure (r s=0.48, p〈0.001 and n=0.42, p=0.001 respectively), while those of intact proinsulin and 32–33 split proinsulin correlated only with diastolic blood pressure (r s=0.33, p=0.009 and r s=0.31, p=0.014 respectively). Using multiple regression analysis, and including age, sex, race and body mass index in the analyses, concentrations of intact proinsulin and 32–33 split proinsulin, but not immunoradiometric assay insulin, were significantly related to diastolic blood pressure. When all three molecules were incorporated into a single model, only 32–33 split proinsulin was related to diastolic blood pressure (F-change=6.91, [5,43 degrees of freedom]; p=0.012). Thus, high concentrations of insulin-like molecules are associated with changes in recognised cardiovascular risk factor in patients with Type 2 (non-insulin-dependent) diabetes mellitus.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    Diabetologia 35 (1992), S. 1170-1172 
    ISSN: 1432-0428
    Schlagwort(e): Myotonic dystrophy ; proinsulin ; insulin resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Hyperinsulinaemia is a reported feature of the inherited multisystem disorder myotonic dystrophy. This phenomenon has been attributed to a compensatory beta cell response to tissue insulin resistance. In this study, circulating concentrations of insulin, proinsulin, and split proinsulin molecules were determined after an overnight fast in ten patients with myotonic dystrophy using two-site monoclonal antibody-based immunoradiometric assays. Results were compared with ten healthy control subjects matched for age, gender, and body mass index. Oral glucose tolerance (75 g), as defined by World Health Organization criteria, was normal in all subjects. Fasting plasma immunoreactive insulin concentration, as determined using a conventional radioimmunoassay, was almost three times higher (p〈0.005) in the myotonic dystrophy patients than the healthy control subjects. By contrast, fasting concentrations (mean±SEM) of C-peptide (0.75±0.09 vs 0.52±0.03 nmol/l, p=0.07) and immunoradiometrically-determined insulin (60±12 vs 38±4 pmol/l, p=0.09) were not significantly different between the groups. Fasting concentrations of proinsulin (10.3±2.9 vs 1.6±0.3 pmol/l, p〈0.01), and 32–33 split proinsulin (7.8±2.5 vs 2.9±0.4 pmol/l, p〈0.05) were significantly elevated in the patients with myotonic dystrophy. Accordingly, the mean fasting proinsulin∶insulin ratio, expressed as a percentage, was significantly increased in the myotonic patients (20±5 vs 4±1%, p〈0.01). The overall C-peptide response to the oral glucose challenge was significantly greater in the myotonic patients compared with the healthy control subjects (p〈0.001). These results provide corroborative evidence of increased beta-cell secretion in myotonic dystrophy. In addition, myotonic dystrophy is characterised by elevated plasma concentrations of proinsulin-like molecules which may cross-react in insulin radioimmunoassays.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of pediatrics 157 (1997), S. S7 
    ISSN: 1432-1076
    Schlagwort(e): Key words Fetal growth ; Blood pressure ; Glucose tolerance ; Programming ; HPA axis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract There is now a large body of evidence to support the hypothesis that events in fetal life permanently alter the structure or function of an individual, programming later adult disease. Reduced birth weight is associated with higher blood pressure in childhood and adult life, and thinness at birth with glucose intolerance and non-insulin dependent diabetes mellitus. Programming of the hypothalamo-pituitary-adrenal (HPA) axis is an attractive hypothesis linking fetal experience and later disease, as an excess of glucocorticoids may be associated with hypertension and glucose intolerance. Moreover, animal data support this hypothesis. Exposing fetal rats to glucocorticoid reduces birth weight and leads to raised blood pressure, as well as to alterations in the HPA axis. Data on the long-term effects of exposure to glucocorticoids in human subjects are limited. Recently, however, reduced size at birth was found to be associated with higher fasting 9 a.m. plasma cortisol concentrations in adults. Raised plasma cortisol concentrations were, in turn, associated with higher blood pressure, and inversely related to measures of glucose tolerance. Conclusion Programming of the HPA axis by events in fetal life may be one of the mechanisms linking reduced size at birth with raised blood pressure and glucose intolerance in later life. Studies of the effects of antenatal and neonatal dexamethasone administration on later blood pressure and glucose tolerance may be warranted.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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