Effects of certain growth factors on in vitro maturation of rat fetal islet-like structures.
We have previously studied the expression of protein tyrosine kinases in different preparations of insulin producing cells by polymerase chain reaction (PCR). Among the tyrosine kinases thus identified were the fibroblast growth factor receptor-4 (FGFR-4), c-Kit, the insulin-like growth factor (IGF-I) receptor, and the cytoplasmic tyrosine kinase Jak2, which associates with the activated receptor for growth hormone (GH). To elucidate the putative biological effects of the receptors identified, fetal islet-like structures were cultured in the absence or presence of the ligands to the receptors identified, namely, acidic FGF (aFGF), stem-cell factor (SCF), IGF-I, and GH, whereafter insulin and DNA contents as well as insulin secretion to the culture medium were determined. Nerve growth factor (NGF), the ligand to the tyrosine kinase receptor Trk-A, was also included. aFGF and GH were found to stimulate insulin release to the culture medium, whereas SCF augmented insulin contents/DNA as well as islet DNA contents. No effects of NGF or IGF-I were detected. Immunohistochemical studies of fetal rat pancreas showed localization of the c-Kit protein to the pancreatic ducts, whereas immuno-reactivity against FGFR-4 could be detected in both endocrine and exocrine parts of the pancreas as well as in the pancreatic ducts. It is concluded that tyrosine kinase receptors may be involved in the maturation of pancreatic beta cells.
Oberg-Welsh
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Department of Medical Cell Biology, Uppsala University, Sweden.
Welsh
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D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology; D005346:Fibroblast Growth Factors; D013006:Growth Hormone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D007150:Immunohistochemistry; D007328:Insulin / Q000032:analysis; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology*; D009414:Nerve Growth Factors / Q000494:pharmacology; D019009:Proto-Oncogene Proteins c-kit / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051499:Receptor, Fibroblast Growth Factor, Type 4; D017468:Receptors, Fibroblast Growth Factor / Q000276:immunology; D019089:Stem Cell Factor / Q000494:pharmacology
D006133:Growth Substances; D007328:Insulin; D009414:Nerve Growth Factors; D017468:Receptors, Fibroblast Growth Factor; D019089:Stem Cell Factor; D016220:Fibroblast Growth Factor 1; D005346:Fibroblast Growth Factors; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D006493:Heparin; D004247:DNA; C496373:Fgfr4 protein, rat; D019009:Proto-Oncogene Proteins c-kit; D051499:Receptor, Fibroblast Growth Factor, Type 4