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  • 1
    ISSN: 1432-0428
    Keywords: Nicotinamide ; Type 1 (insulin-dependent diabetes mellitus ; pre-Type 1 diabetes ; islet-cell antibody ; intravenous glucose tolerance test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A controlled trial of oral nicotinamide to prevent the onset of diabetes mellitus in high risk children was conducted in two centres. The selection criteria were age less than 16 years, islet cell antibody ≥80 IUs, and first phase insulin release 〈 5th percentile. All of eight untreated control subjects have developed diabetes, whereas only 1 of 14 treated children has diabetes to date. This data suggests that nicotinamide has an effect in preventing Type 1 (insulin-dependent) diabetes and that randomized controlled studies are now indicated.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 37 (1994), S. 729-729 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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  • 3
    ISSN: 1420-9071
    Keywords: Insulin ; glucagon ; pancreatic polypeptide ; somatostatin ; fetal pancreas ; ontogeny ; immunocytochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The ontogeny of insulin, glucagon, PP and somatostatin in the mammalian fetal pancreas has been examined in recent years largely by immunocytochemistry and in some instances by radioimmunoassay. Complete ontogenic data are available only for the rat, human pig and sheep. Figure 3 compares the time of appearance of the endocrine cell-types within the fetal pancreas when the periods of gestation of the four species are converted to a uniform scale. The striking ontogenic difference in the rat probably reflects the immaturity of the rodent fetus at birth compared with the human, pig and sheep. In the fetal pancreas, differences in cell number of glucagon and PP cells in the dorsal and ventral lobes become apparent from an early gestational period. Factors responsible for the functional and structural maturation of the fetal pancreatic endocrine cells and the processes involved in pancreatic organogenesis are poorly understood. Studies in these areas would have clinical implications since it may be possible in the future to employ agents for selective replication of fetal β-cells for transplantation in patients with Type I diabetes, bearing in mind that such cells must have the capacity to respond to normal stimuli and repressors when transplanted. The presence of the other islet cell-types may be obligatory for these appropriate responses. This would require a more complete knowledge of those factors which produce the normal selectivity of the four hormonal cell-types.
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Milk ; casein ; epidemiology ; immunosuppression ; beta-casomorphin.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previously published Type I (insulin-dependent) diabetes mellitus incidence in 0 to 14-year-old children from 10 countries or areas was compared with the national annual cow milk protein consumption. Countries which were selected for study had appropriate milk protein polymorphism studies, herd breed composition information and low dairy imports from other countries. Total protein consumption did not correlate with diabetes incidence (r = + 0.402), but consumption of the β-casein A1 variant did (r = + 0.726). Even more pronounced was the relation between β-casein (A1 + B) consumption and diabetes (r = + 0.982). These latter two cow caseins yield a bioactive peptide β-casomorphin-7 after in vitro digestion with intestinal enzymes whereas the common A2 variant or the corresponding human or goat caseins do not. β-casomorphin-7 has opioid properties including immunosuppression, which could account for the specificity of the relation between the consumption of some but not all β-casein variants and diabetes incidence. [Diabetologia (1999) 42: 292–296]
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 12 (1976), S. 15-21 
    ISSN: 1432-0428
    Keywords: Glucose tolerance ; insulin excretion ; juvenile diabetes ; proximal tubule ; radioimmunoassay ; urinary insulin clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A technique is described for the accurate radioimmunoassay of insulin in serum and urine. This method was applied to study of renal clearance and excretion of endogenous and exogenous insulin in untreated juvenile diabetics and healthy young adults. There was good agreement between our results for normal adults and previously reported values. In six non-obese juvenile diabetics, urinary insulin clearance values, both basal (fasting) and following glucose loading (entire range 0.03 ml/min to 1.23 ml/min) were similar to those obtained for the adults (entire range 0.17 ml/min to 2.35 ml/min). The basal urinary excretion in these diabetics was generally of the same order of magnitude as that in the normals. The clearance of exogenous insulin, administered for the first time, was also of the same order as that for endogenous insulin. Markedly elevated urinary clearance and excretion of insulin during fasting and non-fasting states was demonstrated in four non-obese juvenile diabetics with no clinical evidence of abnormal proteinuria, though they demonstrated slight to mild clinical dehydration and acidosis compared with the other diabetics studied. Clearance and excretion of exogenous insulin was similarly elevated. This finding could reflect renal tubular dysfunction in these diabetics, and this dysfunction could relate to even the mild degree of dehydration and acidosis found in this study. Endogenous and exogenous insulin clearance in an obese diabetic child was similar to that for the control group.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 26 (1984), S. 297-299 
    ISSN: 1432-0428
    Keywords: Rat ; pathogenesis ; insulin-dependent diabetes ; dietary proteins ; milk proteins ; wheat proteins
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Animals from a colony of spontaneously diabetic insulin-dependent BB rats were fed from weaning with semisynthetic diets in which natural proteins were replaced by l-amino acids with or without the addition of either milk or wheat proteins. The normal 50% incidence of diabetes in the colony was reduced to 15% in rats fed the basic semi-synthetic diet, while it was 35% and 52% when supplemented with gluten or milk, respectively. Thus, dietary factors might precipitate the expression of the disease.
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  • 7
    ISSN: 1432-0428
    Keywords: BB rats ; intravenous glucose tolerance tests ; first phase insulin release ; immunofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary First phase insulin release was measured in response to intravenous glucose given weekly from approximately day 40 in 6 BB rats which subsequently developed diabetes and in age-matched non-diabetic (n =15) and normal Wistar rats (n = 8) until day 180. The mean sequential insulin responses in BB rats with and without diabetes were significantly lower (p = 0.008 and 〈 0.0001, respectively) than in normal rats from an early age. Five diabetic BB rats showed a progressive decline in first phase insulin release immediately prior to glycosuria, with the impaired phases ranging from 25–50 days. However, protracted periods of low first phase responses were also seen in several aglycosuric BB rats, which showed histological evidence of insulitis and B-cell loss. Our findings demonstrate that, although most BB rats with diabetes show a progressive impairment of B-cell function preceding the disease, this aberrant phase can also be present in BB rats which remain aglycosuric. Impaired first phase insulin release in response to serial intravenous glucose tolerance tests may not be a reliable predictor of Type 1 (insulin-dependent) diabetes in this animal model.
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  • 8
    ISSN: 1432-0428
    Keywords: NOD mouse ; diabetes ; diet ; casein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Diabetes prone NOD female mice were fed diets containing different proteins from just before weaning. Only mice receiving meat meal or casein as the protein source developed diabetes at the rate expected from this colony. Lactalbumin and gluten did not precipitate diabetes except in a small number. Casein hydrolysate in lieu of protein protects against overt diabetes, but only if introduced early. The animals which did not show overt diabetes nevertheless had intermittent trace glycosuria and the majority showed mild degrees of peninsular lymphocytic infiltration.
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  • 9
    ISSN: 1432-0428
    Keywords: NOD mice ; insulitis ; islet cell antibodies ; insulin autoantibodies ; ontogeny ; immunofluorescence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The predictive value of insulitis, islet cell cytoplasmic antibodies and insulin autoantibodies for insulin-dependent diabetes was studied in young female non-obese diabetic mice. The ontogeny of the three markers was examined cross-sectionally at days 15, 25, 40 and 90 while islet cell antibodies and insulin autoantibodies were studied longitudinally from day 35 or day 144–168 until approximately day 250. Insulitis was first observed at day 40 (50%) and subsequently at day 90 (70%). Islet cell antibodies and insulin autoantibodies were present at day 15 in 46% and 54% of the animals respectively. The rate of islet cell antibodies was slightly higher at day 25 (60%) than at day 40 (40%) and day 90 (54%) whereas antibodies to insulin were present in all samples from day 25–90. At day 40 and day 90 insulitis and insulin autoantibodies were present together in 42% and 70% of the animals, respectively, while insulitis and islet cell antibodies had a lower rate of concordance (17% and 42%, respectively; diabetes rate, 30%). The concordance rates for islet cell antibodies and insulin autoantibodies were 42% at day 40 and 54% at day 90. Concordance for all three markers was first observed at day 40 (17%) which increased to 38% at day 90. In longitudinal studies, islet cell antibodies and insulin autoantibodies were often present together whether or not diabetes supervened. In the islet cell antibody procedure, immunoreactive cells were shown immunohistochemically to correspond with insulin and/or glucagon cells. However, this staining was not suppressible with insulin- or glucagon- absorbed sera, implying the presence of non-hormonal autoantigens. We conclude that the three markers investigated are expressed early after birth and well before clinical symptoms appear in this animal model. Both islet cell antibodies and insulin autoantibodies preceded insulitis but the prevalence rate for each marker or their degree of concordance was different from the anticipated rate of diabetes in our colony. Consequently, the early expression of the three markers alone is not predictive of diabetes although concordance for the two, or all three markers may be of some value. However, no animal developed diabetes without the prior appearance of both islet cell antibodies and insulin autoantibodies.
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  • 10
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
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