Diabetes
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Hepatocyte Growth Factor/Scatter Factor Has Insulinotropic Activity in Human Fetal Pancreatic Cells Fetal mesenchyme-derived factors are likely to play an important role in pancreatic islet development and growth. We have used primary cultures of human fetal pancreatic tissue to identify growth factors that have morphogenic, mitogenic, and insulinotropic activity. The formation of islet-like cell clusters (ICCs) during a 6-day culture was stimulated two- to threefold by hepatocyte growth factor/scatter factor (HGF/SF) basic fibroblast growth factor (FGF)-2, and to a lesser extent by keratinocyte growth factor (FGF-7) and insulin-like growth factor-II (IGF-II). In contrast, transforming growth factor-β (TGF-β) had a strong inhibitory effect. The ICCs formed during HGF/SF stimulation consisted mainly of epithelial cells, whereas FGF-2-induced ICCs were predominantly nonepithelial. Furthermore, although both FGF-2 and HGF/SF increased the total insulin content of the cultures, only HGF/SF increased the insulin content per DNA. Quantitatively, HGF/SF stimulated a 2.3-fold increase in the proportion of insulin-positive cells and a 3-fold higher number of replicating β-cells. Blocking of the IGF-I receptor inhibited ICC formation but did not affect their insulin content. Immunoneutralizing TGF-β resulted in increased cell growth and insulin content, indicating the presence of an endogenous inhibitory TGF-β activity in the model system. Our results suggest that HGF/SF may be an important component of the fetal mesenchyme-derived factors responsible for pancreatic islet development. HGF/SF also may prove valuable for supporting the in vitro growth of islet cells.
Diabetes - Tập 43 Số 7 - Trang 947-953 - 1994
Expression of Functional Nerve Growth Factor Receptors in Pancreatic β-cell Lines and Fetal Rat Islets in Primary Culture Previous data demonstrated that one rat insulinoma cell line, RINm5F cells, which is a rat β-cell line derived from a pancreatic tumor, express mRNA coding for both the low- and the high-affinity nerve growth factor receptors. Goals of this study were to extend our data to other β-cell lines and fetal islets in primary culture and to study further the binding characteristics of nerve growth factor receptors on β-cells. Northern blot analysis revealed that not only a panel of endocrine β-cell lines (RINm5F, INS-1, β-TC3) but also fetal rat islets in primary culture express mRNA coding for trk-A, which has been proposed to be the neuronal high-affinity nerve growth factor receptors. Reverse polymerase chain reaction followed by sequencing revealed that the sequence of trk-A receptor in RINm5F cells is identical to that of trk-A expressed in PC12 cells. The expression of the low-affinity nerve growth factor receptor was examined by Northern blot analysis that showed low-affinity nerve growth factor receptor to be expressed in RINm5F and INS-1 cell lines, in fetal rat islets in primary culture, but not in β-TC3-cells. Binding experiments revealed the presence of low- and high-affinity nerve growth factor binding sites, identical to those described for PC12 cells, on RINm5F and INS-1 cells and only high-affinity binding sites on β-TC3 cells. Exposure of all three β-cell lines to nerve growth factor increased NGFI-A and c-fos mRNA steady-state levels, showing that these receptors are functional. These data demonstrate that the entire machinery required for nerve growth factor action is present in β-cells in culture.
Diabetes - Tập 42 Số 12 - Trang 1829-1836 - 1993
Autoantibodies to protein tyrosine phosphatase-like proteins in type I diabetes. Overlapping specificities to phogrin and ICA512/IA-2
Diabetes - Tập 45 Số 10 - Trang 1344-1349 - 1996
HLA heterogeneity of insulin-dependent diabetes mellitus at diagnosis. The Pittsburgh IDDM study
Diabetes - Tập 34 Số 12 - Trang 1247-1252 - 1985
Value of antibodies to islet protein tyrosine phosphatase-like molecule in predicting type 1 diabetes
Diabetes - Tập 46 Số 8 - Trang 1270-1275 - 1997
Pancreatic islet cell cytoplasmic antibody in diabetes is represented by antibodies to islet cell antigen 512 and glutamic acid decarboxylase
Diabetes - Tập 44 Số 11 - Trang 1290-1295 - 1995
Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity
Diabetes - Tập 43 Số 10 - Trang 1254-1259 - 1994
Prediction of IDDM in the general population: strategies based on combinations of autoantibody markers
Diabetes - Tập 46 Số 11 - Trang 1701-1710 - 1997
Diabetes Antibody Standardization Program: First Assay Proficiency Evaluation The aims of the first proficiency evaluation of the Diabetes Antibody Standardization Program (DASP) were to assess general implementation of assay methods and to evaluate the new World Health Organization (WHO) reference reagent for autoantibodies to GAD and IA-2. Forty-six laboratories in 13 countries received coded sera from 50 patients with newly diagnosed type 1 diabetes and 50 blood donor control subjects, together with the WHO reference reagent and diluent serum. Results were analyzed using receiver operator characteristic (ROC) curves. Sensitivity was adjusted to 90% specificity in workshop controls. The median adjusted sensitivity for GADA (45 laboratories) was 84% (range 62–96%), for IA-2A (43 laboratories) was 58% (50–74%), and for insulin autoantibody (IAA; 23 laboratories) was 36% (13–66%). ROC curve analysis showed all GADA and IA-2A assays, and 18/23 IAA assays found significant differences between patients and control subjects. There was good concordance between laboratories in ranking of samples by GADA and IA-2A levels or if results were expressed in relation to the WHO reference reagent. Assays that achieved the highest sensitivity for IAA were also concordant in ranking samples, but overall concordance for IAA was poor. Differences in assay protocols between laboratories must be addressed so that all centers and kit manufacturers can perform to the same high standard.
Diabetes - Tập 52 Số 5 - Trang 1128-1136 - 2003
Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies
Diabetes - Tập 45 Số 7 - Trang 926-933 - 1996
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