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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 59-59 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Porcine NPH insulin ; semi-synthetic and biosynthetic human NPH insulin ; pharmacokinetics ; pharmacodynamics ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, ‘semi-synthetic’ and ‘biosynthetic’ human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the ‘intermediate-acting’ NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 28 (1985), S. 32-37 
    ISSN: 1432-0428
    Keywords: Peripheral hyperinsulinaemia ; aorta metabolism ; muscle metabolism ; tissue triglycerides ; enzyme activities ; macrovascular disease ; pig
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Peripheral hyperinsulinaemia usually found in conventionally treated Type 1 (insulin-dependent) diabetic patients may have deleterious metabolic effects. We have used a hyperinsulinaemic model to examine intermediary metabolism in two key peripheral tissues, aorta and muscle. Nine pigs were immunized with crystalline insulin. Subsequently, they showed an insulin-binding capacity of 86.2±25.0 pmol/l and fasting total serum insulin of 3.9±3.1 nmol/l (control range 0.034–0.072 nmol/l), impaired glucose tolerance after oral glucose tolerance testing, significantly elevated levels of peripheral venous serum free insulin and C-peptide, and increased mean post-prandial free insulin/glucose ratios. The immunized pigs showed marked elevation of aorta and muscle triglycerides compared with control pigs (n = 15) but similar levels of non-esterified fatty acids. The glucose-6-phosphate-dehydrogenase, malic enzyme and 3-hydroxyacyl-CoA-dehydrogenase activities were all increased significantly (by 50%–300%) in both aorta and muscle. Phosphofructokinase was decreased in both tissues. Hexokinase was increased in muscle alone whereas pyruvate kinase was significantly decreased in aorta. Glyceraldehyde-3-phosphate dehydrogenase activity was not significantly different in aorta and muscle. Thus in insulin immunized pigs with normal β-cell function and pronounced peripheral hyperinsulinaemia there was increased peripheral lipogenic activity. These findings have potentially important implications with regard to macrovascular disease in diabetes.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 571-577 
    ISSN: 1432-0428
    Keywords: Insulinoma ; malignant insulinoma ; proinsulin ; C-peptide ; insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The value of plasma insulin, human C-peptide and proinsulin estimation in the diagnosis of 15 insulinomas has been investigated. Measurement of plasma proinsulin in an overnight fasting sample diagnosed all the insulinomas studied, irrespective of the plasma glucose. Patients with insulinomas had plasma proinsulin in the range 0.04–4.2 pmol/l and normal values were less than 0.01 pmol/ml. If hypoglycaemia was present, an inappropriately raised plasma immunoreactive insulin (including proinsulin) was diagnostic, but this assay was of little assistance if the plasma glucose was normal. Hypoglycaemia was induced with fish insulin in twelve patients with insulinomas and eight normal subjects. Using an antiserum which did not detect fish insulin, but cross-reacted with human proinsulin, the endogenous immunoreactive insulin was suppressed in the normal subjects, but all insulinoma patients had impaired suppression. Assay of plasma human C-peptide, or of the combined immunoreactive C-peptide and proinsulin, discriminated less well and did not clearly diagnose three insulinomas which secreted proinsulin rather than insulin and C-peptide. Plasma human proinsulin values during induced hypoglycaemia gave excellent discrimination and should detect insulinomas irrespective of their degree of histological differentiation. The assay of plasma human proinsulin allows a suppression test to be performed with hypoglycaemia induced by any type of insulin. A raised plasma proinsulin in proportion to C-peptide suggests an undifferentiated insulinoma, which may be more likely to be malignant.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Diabetes ; antidiabetic biguanides ; blood glucose ; plasma pancreatic GLI ; plasma gut GLI ; intraduodenal glucose administration ; intraduodenal amino acid administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Five patients with mild maturity-onset diabetes were given 250 ml of a 20% glucose solution by intraduodenal infusion and eight other patients similarly received an amino acid solution in a dose of 0.5 g amino acids per kg body weight. The pancreatic and gut glucagon-like immunoreactivity (pancreatic GLI and gut GLI) in plasma were measured before and after the application of the two stimuli. Each person was tested twice; the first (control) test was followed by a second test after three days of treatment with phenformin 150 mg daily, plus the same 150 mg dose taken 60 min before the intubation. The plasma pancreatic GLI increased slightly during both infusions, but was not affected by phenformin. Intraduodenal infusion of both glucose and the amino acid solution induced a greater rise in plasma gut GLI. After treatment with phenformin, the fasting plasma gut GLI was higher than the control value in eleven of thirteen patients. In most cases higher gut GLI plasma levels were also found after duodenal administration of glucose and amino acids. These data furnish further evidence of the local action of antidiabetic biguanides on the intestinal wall, including its hormonal activity. The hypothesis is advanced that the phenformin-induced increase in gut GLI secretion may bring about competition of the latter with pancreatic glucagon for receptors in liver cell membranes, reducing the effect of glucagon on the liver, and thus contributing to a decrease in glycaemia.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 21 (1981), S. 103-107 
    ISSN: 1432-0428
    Keywords: Thyrotoxicosis ; insulin secretion ; proinsulin ; C-peptide ; insulin immunoreactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma insulin, C-peptide and proinsulin concentrations were investigated in thyrotoxic patients and in normal controls after an overnight fast, during a 36 h fasting period, an intravenous glucose tolerance test and an oral glucose tolerance test. The main finding was a significantly raised concentration of proinsulin in plasma of patients with thyrotoxicosis. After an overnight fast the plasma proinsulin was 0.048±0.005 pmol/ml in 15 thyrotoxic patients compared with 0.023±0.012 pmol/ml in 15 euthyroid controls. A twofold rise of plasma proinsulin concentration was also found in thyrotoxic patients during a prolonged fast, and during intravenous and oral glucose tolerance tests. The immunoreactivity of proinsulin in the insulin radioimmunoassay gave rise to slightly elevated concentrations of immunoreactive insulin in thyrotoxic patients in all the conditions investigated. When insulin values were corrected for proinsulin crossreactivity, they were similar in euthyroid controls and thyrotoxic patients. The concentration of plasma C-peptide was not significantly altered in thyrotoxic patients during intravenous and oral glucose tolerance tests.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 627-630 
    ISSN: 1432-0428
    Keywords: Juvenile diabetes ; C-peptide ; remission ; ketonuria ; insulin antibodies ; total IRI
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum C-peptide, insulin-binding IgG and total insulin (IRI) were determined in 96 juvenile diabetics aged 4–21 years, with onset of diabetes at the age of 1–16 years and with 2–17 years' duration of diabetes. Thirty-four patients (35.4%) had detectable levels of C-peptide (≥ 0.04 pmol/ml). Compared to non-diabetic adults, 19 had values below the normal range, 12 showed values within the normal range (0.18–0.63 pmol/ml) and 3 rated above normal. There was a negative correlation between the fasting C-peptide concentration and the degree of ketonuria at the onset of diabetes and a positive correlation between C-peptide levels and the incidence of postinitial remission periods. Patients without detectable C-peptide had significantly higher levels of insulin antibodies than those who had detectable levels of C-peptide. The possibility of a relationship between the intensity of the initial treatment of diabetes and the preservation of the B-cell function is discussed, as well as the possibility of insulin antibodies being a cause of B-cell exhaustion.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 13 (1977), S. 467-474 
    ISSN: 1432-0428
    Keywords: Radioimmunoassay ; human proinsulin ; insulin ; C-peptide ; oral glucose ; diabetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A routine radioimmunoassay for human proinsulin in serum has been developed. The reagents used were: antibodies against the C-peptide part of the proinsulin molecule, human proinsulin as the standard and125I-labelled synthetic human Tyr-C-peptide as the tracer. The first step in this assay comprises the binding of proinsulin to insulin antibodies covalently coupled to Sepharose (S-AIS). Although bound to the solid-phase S-AIS, the proinsulin retains its second immunogenic site, viz., the C-peptide part of the molecule, accessible. Hence a surplus of C-peptide antibodies is added to the S-AIS-bound proinsulin, and the residual amount of C-peptide antibody is determined by addition of125I-Tyr-C-peptide. The detection limit is approximately 0.01 pmol/ml. The advantages of this method are: (1) its high specificity (proinsulin is determined as a molecule having both an insulin and a C-peptide moiety), (2) its simplicity and rapid performance, and (3) the low detection limit of the assay. Fasting sera from 24 nondiabetics, 9 maturityonset diabetics and 10 newly diagnosed insulin requiring diabetics showed the following concentrations of proinsulin: 0.009±0.005, 0.022±0.23 and 0.010±0.009 pmol/ml (mean±SD). One hour after 1.75 g/kg oral glucose, the values increased to 0.052±0.023, 0.046±0.022 and 0.032±0.022 pmol/ml. The fasting proinsulin constituted 19, 23 and 17% of the IRI, respectively, whereas 1 h post glucose these values changed to 8, 9 and 31% of IRI. Serum from 10 insulin-treated diabetics containing insulin antibodies contained from 0–1.80 pmol/ml, whereas the C-peptide levels in the same patients were 0–0.35 pmol/ml. It is suggested that insulin requiring diabetics hypersecrete proinsulin due to the inability of their B-cell to arrange proinsulin in secretory granules for adequate proinsulin/insulin conversion.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-0428
    Keywords: Insulin antibodies ; proinsulin antibodies ; pancreatic polypeptide antibodies ; a-component antibodies ; total serum immunoreactive insulin ; insulin immunogenicity ; insulin-dependent diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Ninety-two insulin-dependent diabetics (aged 4–20 years, mean±SD: 13±4) with a duration of diabetes from 2 to 17 years (7±3) were transferred from Lente or NPH (5 × crystallised insulin) to Monotard insulin (highly purified insulin). Total serum immunoreactive insulin levels and concentrations of antibodies against insulin, porcine proinsulin, a-component and pancreatic polypeptide were determined prior to [I] and at a mean of 220 [II], 460 [III], 830 [IV], and 1170 [V] days after the change. All but two subjects had insulin antibodies (IgG) at the start, with a mean value of 2864 μU/ml. There was a significant fall in the mean insulin antibody level between [I] and [II] to 2165 μU/ml (p〈10-7), followed by an increase between [II] and [III] whereafter a slight decrease was observed being significant between [III] and [IV], as well as between [IV] and [V] (p〈0.05); some patients showed a constant fall over the entire period, while others showed fluctuations. Total serum insulin showed a similar pattern, with a mean value of 1141 μU/ml at [I] declining to 522 μU/ml at [V]. The percentage fall between [I] and [V] was greater (54%) than that in the insulin antibodies (30%). Antibodies against acomponent, proinsulin and pancreatic polypeptide were present in 96%, 72% and 41% of the patients respectively before the change in therapy. There was a decline in these antibodies between each sampling (p values between 〈10-3 and 10-8) and, at the end of the investigation antibodies against a-component were above the detection limit in only 4 patients, and none of the patients showed antibodies against proinsulin or pancreatic polypeptide. Thus, removal of the impurities, including the hormonal contaminants of insulin, leads to a slow fall in antibodies to insulin and a much faster disappearance of antibodies against acomponent, proinsulin and pancreatic polypeptide.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-0428
    Keywords: Human proinsulin ; radioimmunoassay ; standards
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two new batches of pancreatic human proinsulin have been compared with biosynthetic human proinsulin. Standards of these three proinsulin preparations were made on the basis of quantitative amino-acid analyses and compared in two proinsulin radioimmunoassays with a proinsulin standard prepared 14 years ago. The curves of the new standards were superimposable. However, they differed considerably from the curve of the old standard which proved to be only one-third of the strength of the new standards, thereby leading to a threefold over-estimation of proinsulin concentrations when the old standard is used. We conclude that the new standards should replace previously used standards.
    Type of Medium: Electronic Resource
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