![]() ![]() These results provide insights into the mechanisms whereby HNF-1alpha affects beta-cell function.Ġ1: Supplemental Data 2. ![]() Furthermore expression profiling studies using immortalized cell lines generated from HNF-1alpha/RIP-Tag mice showed changes in expression of genes involved in cellular growth and proliferation. Our results indicate that deficiency of HNF-1alpha severely constrains the extent of beta-cell proliferation occurring in RIP-Tag mice leading to significant changes in blood glucose concentrations as a result of reduced beta-cell number, insulin content, insulin secretion and intracellular responses in Ca(2+). The resulting mouse strains allowed us to study the effect of HNF-1alpha deficiency on the extensive beta-cell proliferation that occurs in these mice. Mice lacking one allele of the HNF-1alpha gene were crossed with transgenic mice expressing the large T antigen driven by the rat insulin II promoter (RIP). In order to explore the relationship between HNF-1alpha and beta-cell proliferation, we have created a novel animal model. The mechanisms responsible for defective glucose-induced insulin secretion due to HNF-1alpha deficiency are complex. Humans heterozygous for mutations in the HNF-1alpha gene develop maturity-onset diabetes of the young (MODY3), which is associated with reduced insulin secretion. Hepatocyte nuclear factor (HNF)-1alpha is a homeodomain-containing transcription factor.
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