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Effects of certain growth factors on in vitro maturation of rat fetal islet-like structures
1Department of Medical Cell Biology, Uppsala University, Sweden.
Abstract:
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.
Insights
Tyrosine kinase receptors like FGFR-4 and c-Kit influence pancreatic beta cell development. Growth factors such as acidic FGF and GH stimulate insulin release, while stem-cell factor enhances insulin and DNA content in developing islets.
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Protein tyrosine kinases are crucial for cellular signaling.
- Previous studies identified specific tyrosine kinases (FGFR-4, c-Kit, IGF-I receptor, Jak2) in insulin-producing cells.
Purpose of the Study:
- To investigate the biological effects of identified tyrosine kinase receptors on fetal islet-like structures.
- To explore the role of specific ligands (aFGF, SCF, IGF-I, GH, NGF) in pancreatic beta cell function and development.
Main Methods:
- Culture of fetal islet-like structures with specific receptor ligands.
- Measurement of insulin and DNA content, and insulin secretion.
- Immunohistochemical analysis of fetal rat pancreas for receptor localization.
Main Results:
- Acidic FGF and GH significantly stimulated insulin secretion.
- Stem-cell factor increased insulin content/DNA and islet DNA content.
- NGF and IGF-I showed no significant effects on the measured parameters.
- Immunohistochemistry revealed c-Kit in pancreatic ducts and FGFR-4 in endocrine, exocrine pancreas, and ducts.
Conclusions:
- Tyrosine kinase receptors, particularly those activated by aFGF and GH, play a role in regulating insulin secretion.
- SCF influences insulin content and islet proliferation.
- These findings suggest tyrosine kinase receptors are involved in pancreatic beta cell maturation.