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  • 1
    Electronic Resource
    Electronic Resource
    Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark (1977)
    Springer
    Diabetologia 13 (1977), S. 281-284 
    Details
    ISSN: 1432-0428
    Keywords: Incidence ; seasonal variation ; geographical pattern ; sex-difference ; epidemiology ; juvenile-onset ; insulin-dependent ; diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970–1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27 per cent. A marked peak of incidence was found at 12–14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May–July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01223266
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  • 2
    Electronic Resource
    Electronic Resource
    Virus-induced diabetes mellitus in mice and the thymus-dependent immune system (1983)
    Springer
    Diabetologia 24 (1983), S. 42-46 
    Details
    ISSN: 1432-0428
    Keywords: Encephalomyocarditis virus ; diabetes mellitus ; athymic nude mice ; the thymus-dependent immune system ; cyclophosphamide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study concerns the effect of the experimental diabetogenic encephalomyocarditis (EMC) virus on normal and athymic nude mice of BALB/c origin. The effect of simultaneous immunosuppressive pharmacological treatment with a derivative of cyclophosphamide in a relatively low dose (3 mg/mouse) was also studied. After inoculation with EMC virus, 36% of the normal mice, but none of the nude mice, developed diabetes mellitus and 93% of the normal mice, but none of the nude mice, developed paresis of one or more leg(s). When lower doses of EMC virus were given, few or none of the normal mice developed diabetes or paresis. After treatment with a cyclophosphamide-derivative, the number of paralysed mice increased. EMC virus in abundant amounts could be isolated from the pancreas and heart of all virus-inoculated mice, including the non-diabetic nude mice. Antibodies against EMC virus were found in all groups of virus-inoculated mice, although only in small amounts in nude and immunosuppressed normal mice. Histological examination revealed no significant differences between the islets of Langerhans of the experimental mice, diabetic as well as non-diabetic, and the control mice with respect to lymphocytic infiltration. It is concluded that the thymus-dependent immune system seems to be of decisive importance for the development of diabetes in this virus model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00275946
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  • 3
    Electronic Resource
    Electronic Resource
    Presence of sulphatide (3 ′-sulphogalactosylceramide) in pericytes in the choroid layer of the eye: sharing of this glycolipid autoantigen with islets of Langerhans (1996)
    Springer
    Diabetologia 39 (1996), S. 658-666 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Sulphatide ; glycolipid ; pericytes ; choroid layer ; eye.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the study was to investigate the distribution in the eye of sulphatide, an acid glycolipid which has previously been demonstrated in islets of Langerhans, nervous tissue and in kidney glomeruli of diabetic patients, and against which antibodies have been found in patients with newly diagnosed insulin-dependent diabetes mellitus. A specific monoclonal antibody, Sulph I, was used for detection of sulphatide by thin-layer chromatography, and light and electron microscope immunohistochemistry. A distinct, patchy staining was found in the choroid layer and the ciliary processes. The antigen was confirmed to be sulphatide and its concentration in human eyes was 30 nmol sulphatide/g wet tissue. By electron microscopy, anti-sulphatide choroid labelling was demonstrated in pericytes and in smooth muscle cells surrounding vessels. No Sulph I-negative pericytes were seen. Double labelling with Sulph I and anti-smooth muscle actin revealed that only pericytes in the eye contained sulphatide and not those in heart, lung, liver, adrenal, spleen, lymph node, thymus, or pancreatic tissue. Thus, sharing of the autoantigen sulphatide has been demonstrated between islets of Langerhans and pericytes in the choroid layer of the eye. [Diabetologia (1996) 39: 658–666]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418537
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  • 4
    Electronic Resource
    Electronic Resource
    The insulinotropic effect of endothelin-1 is mediated by glucagon release from the islet alpha cells (1999)
    Springer
    Diabetologia 42 (1999), S. 1302-1307 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Endothelin-1 ; insulin secretion ; glucagon secretion ; flow cytometry ; alpha cell ; beta cell ; clonal cell line ; endothelin receptor ; gene expression.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. The circulating concentrations of endothelin-1 (ET-1), a peptide derived from endothelium, are increased in hypertension and diabetes. Endothelin-1 has recently been shown to be an insulinotropic agent. The mechanism of action of endothelin-1 on the endocrine pancreas has not yet been clarified. Methods. We investigated the action of endothelin-1 on the insulin secretion, the binding of 125I-ET-1 to beta cells as well as its effects on purified beta and non-beta cells from normal rats. The expression of endothelin receptors in alpha- and beta-cell lines and in normal rat islets was also studied. Results. First, we studied the effects of endothelin-1 on insulin secretion from beta-cell lines (INS-1, βTC3 and MIN6). At all endothelin-1 concentrations applied (1 pmol/l to 1 μmol/l) no change in insulin secretion was found. Ligand-binding experiments on βTC3 cells showed no specific binding of 125I-ET-1. A prominent expression of ETA-receptor mRNA in an alpha-cell line (αTC1.9) and in normal rat islets was found whereas no expression was found in INS-1 cells. No influence of endothelin-1(1 μmol/l) on insulin secretion stimulated by glucose was detected from purified beta cells. Endothelin-1-(100 nmol/l) increased, however, both insulin and glucagon secretion from a mixture of purified beta and non-beta cells indicating that alpha cells seem to have a key role for the action of ET-1 on insulin secretion. Conclusion/interpretation. The insulinotropic impact of endothelin-1 is not caused by a direct action on the beta cells but seems to be mediated by a paracrine action, probably secondary to enhanced release of glucagon from the endothelin receptor positive alpha cells. [Diabetologia (1999) 42: 1302–1307]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051442
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  • 5
    Electronic Resource
    Electronic Resource
    Inhibition of insulin-specific autoreactive T-cells by sulphatide which is variably expressed in beta cells (1999)
    Springer
    Diabetologia 42 (1999), S. 1212-1218 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes mellitus ; insulin ; autoreactive T-cells ; sulphatide ; beta cells.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Sulphatide and insulin are present in the secretory granules and at the surface of beta cells in islets of Langerhans. Insulin autoantibodies and T-cell reactivity against insulin exist during the development of Type I (insulin-dependent) diabetes during which active beta cells may be more vulnerable than passive. Our aims were to examine the presence of sulphatide in active and passive beta cells and to clarify whether sulphatide influences the direct autoimmunity against insulin. Methods. We incubated rat islets in 2.8, 11.0 or 20.0 mmol/l glucose for 24 h and did an electron microscopic evaluation after labelling with a specific anti-sulphatide monoclonal antibody. The reactivity of an insulin-specific T-cell clone isolated from a patient with Type I diabetes, was examined using insulin or insulin B-chain (B11–27) peptide incubated together with sulphatide. Results. We detected lower amounts of sulphatide per insulin secretory granule in active compared with passive beta cells (p = 0.003). The presence of sulphatide in vitro at doses of 43–8.3 μmol/l resulted in greatly reduced proliferation (median 3.4 % of control value, p = 0.0004) of the insulin-specific T-cell clone. No inhibition was found using the precursor of sulphatide, galactosylceramide, or GM1. Sulphatide did not reduce non-aspecific proliferation (induced by phorbol myristate acetate plus anti-CD3) or specific proliferation induced by insulin peptide. Conclusion/interpretation. These results imply that sulphatide possibly affect processing of the insulin molecule. Sulphatide which has been reported to interfere with phagosome-lysosome fusion, conceivably interacts with insulin. We hypothesize a (patho)physiological role of sulphatide, variably expressed in beta cells, by reducing the antigenicity of insulin. [Diabetologia (1999) 42: 1212–1218]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051294
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  • 6
    Electronic Resource
    Electronic Resource
    Sulphatide in islets of Langerhans and in organs affected in diabetic late complications: a study in human and animal tissue (1994)
    Springer
    Diabetologia 37 (1994), S. 1000-1006 
    Details
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; glycolipids ; sulphatide ; islets of Langerhans ; kidney ; peripheral nerves ; eye ; ovary ; thin-layer chromatography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150±46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules. Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400463
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  • 7
    Electronic Resource
    Electronic Resource
    Sulphatide in islets of Langerhans and in organs affected in diabetic late complications: a study in human and animal tissue (1994)
    Springer
    Diabetologia 37 (1994), S. 1000-1006 
    Details
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; glycolipids ; sulphatide ; islets of Langerhans ; kidney ; peripheral nerves ; eye ; ovary ; thin-layer chromatography.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Sulphatide has been found in rat islets of Langerhans and anti-sulphatide antibodies have been demonstrated in patients with insulin-dependent diabetes mellitus. Using a specific monoclonal antibody, Sulph I, directed against sulphatide, we investigated the in situ distribution of this glycolipid immunohistochemically; furthermore, the sulphatide concentration was determined in several organs and cells by thin-layer chromatography. The islets of Langerhans in all species examined, mouse, rat, pig, and monkey were intensively stained but exocrine tissue remained unlabelled. The sulphatide concentration in human islets was 150 ± 46 pmol/100 islets. The only glycolipid-antigen detected was sulphatide. Regarding other tissues, sulphatide was found to be located in distal tubules in the kidney, peripheral nerves, distinct scattered spot-like structures in the choreoid layer of the eye, the ovum, and peripheral granulocytes. Sulph I injection in mice showed homing to kidney tubules. Lung, heart, liver, adrenal, spleen, lymph node and thymus were not stained by Sulph I. Thus, the distribution of sulphatide shows an association with organs known to be affected in diabetes, either initially or in late complications. [Diabetologia (1994) 37: 1000–1006]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400463
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  • 8
    Electronic Resource
    Electronic Resource
    Glucose induces early growth response gene (Egr-1) expression in pancreatic beta cells (1999)
    Springer
    Diabetologia 42 (1999), S. 195-203 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Glucose stimulation ; beta-cell line ; MIN6 ; transcription factor ; Egr-1.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A copy deoxyribonucleic acid (cDNA) clone of the immediate early growth response gene, egr-1 (Krox-24, Zif268, NGFI-1), was isolated through subtractive hybridization screening to identify glucose-induced genes in pancreatic beta cells. Glucose rapidly and transiently induced egr-1 mRNA in the SV40-transformed murine beta-cell line, MIN6. Glucose also increased egr-1 mRNA expression in INS-1, βTC3 and RINm5F beta-cell lines, although with different kinetics. Expression of the 82 kDa Egr-1 protein was induced both in MIN6 cells stimulated with glucose in vitro and in primary rat islet cells stimulated in vivo or in vitro. This response is unique to beta cells since glucose did not affect egr-1 expression in NIH-3T3 fibroblasts or glucose-sensitive hepatocytes. In beta cells egr-1 induction is specifically associated with insulin secretion, as it was not observed after stimulation with serum or insulin but was elicited by insulin secretagogues, including membrane depolarizing agents and cAMP agonists. Moreover, induction of egr-1 by glucose was inhibited by EDTA, indicating dependence on influx of extracellular Ca2+. Other immediate early response genes, c-fos and junB, were also induced following glucose stimulation with kinetics similar to egr-1, whereas c-jun and junD expression were not affected. Since the zinc-finger protein encoded by egr-1 is highly homologous to transcription factors that control expression of glucose-regulated genes in yeast, Egr-1 could mediate delayed adaptive responses of beta cells to sustained glucose stimulation through transcriptional regulation. [Diabetologia (1999) 42: 195–203]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250051139
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  • 9
    Electronic Resource
    Electronic Resource
    Presence of sulphatide (3′-sulphogalactosylceramide) in pericytes in the choroid layer of the eye: sharing of this glycolipid autoantigen with islets of Langerhans (1996)
    Springer
    Diabetologia 39 (1996), S. 658-666 
    Details
    ISSN: 1432-0428
    Keywords: Sulphatide ; glycolipid ; pericytes ; choroid layer ; eye
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of the study was to investigate the distribution in the eye of sulphatide, an acid glycolipid which has previously been demonstrated in islets of Langerhans, nervous tissue and in kidney glomeruli of diabetic patients, and against which antibodies have been found in patients with newly diagnosed insulin-dependent diabetes mellitus. A specific monoclonal antibody, Sulph I, was used for detection of sulphatide by thin-layer chromatography, and light and electron microscope immunohistochemistry. A distinct, patchy staining was found in the choroid layer and the ciliary processes. The antigen was confirmed to be sulphatide and its concentration in human eyes was 30 nmol sulphatide/g wet tissue. By electron microscopy, anti-sulphatide choroid labelling was demonstrated in pericytes and in smooth muscle cells surrounding vessels. No Sulph I-negative pericytes were seen. Double labelling with Sulph I and anti-smooth muscle actin revealed that only pericytes in the eye contained sulphatide and not those in heart, lung, liver, adrenal, spleen, lymph node, thymus, or pancreatic tissue. Thus, sharing of the autoantigen sulphatide has been demonstrated between islets of Langerhans and pericytes in the choroid layer of the eye.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418537
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  • 10
    Electronic Resource
    Electronic Resource
    GAD65 autoantibodies in women with gestational or insulin dependent diabetes mellitus diagnosed during pregnancy (1996)
    Springer
    Diabetologia 39 (1996), S. 1329-1333 
    Details
    ISSN: 1432-0428
    Keywords: Keywords GAD65 ; IAA ; ICA ; HLA ; gestational diabetes ; pregnancy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the presence of GAD65 autoantibodies in women with insulin-dependent diabetes mellitus (IDDM) (n = 28) or gestational diabetes (GDM) (n = 139) diagnosed during pregnancy and investigated the temporal relationship between these autoantibodies and the subsequent recurrence or development of IDDM. Among the GDM patients, 4.3 % (6 of 139) developed true IDDM during a median follow-up period of 6.3 years (range 4.0–11.0). Of these, 2.2 % (3 of 139) were positive for GAD65 autoantibodies at diagnosis of GDM compared to 0 % (0 of 27) of healthy pregnant women. All 3 GAD65 autoantibody positive GDM patients subsequently developed IDDM after a median of 14 months (range 4–34). GAD65 autoantibodies were present in 50 % (14 of 28) of sera from women with IDDM diagnosed during pregnancy. The non-insulin-requiring remission period was significantly shorter in GAD65 autoantibody positive patients (median 0.5 years [range 0–6.0 years]) than in GAD65 antibody negative patients (median 2.6 years; range 0–9.7 years; p 〈 0.05). The results suggest that screening for GAD65 autoantibodies in women with GDM or IDDM diagnosed during pregnancy may be useful for predicting the clinical course of the disease. [Diabetologia (1996) 39: 1329–1333]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050578
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