In rats, the time of birth is characterized by a transient rise in beta cell replication, as well as beta cell neogenesis and the functional maturation of the endocrine pancreas. However, the knowledg Show more
In rats, the time of birth is characterized by a transient rise in beta cell replication, as well as beta cell neogenesis and the functional maturation of the endocrine pancreas. However, the knowledge of the gene expression during this period of beta cell expansion is incomplete. The aim was to characterize the perinatal rat pancreas transcriptome and to identify regulatory pathways differentially regulated at the whole organ level in the offspring of mothers fed a regular control diet (CO) and of mothers fed a low-protein diet (LP). We performed mRNA expression profiling via the microarray analysis of total rat pancreas samples at embryonic day (E) 20 and postnatal days (P) 0 and 2. In the CO group, pancreas metabolic pathways related to sterol and lipid metabolism were highly enriched, whereas the LP diet induced changes in transcripts involved in RNA transcription and gene regulation, as well as cell migration and apoptosis. Moreover, a number of individual transcripts were markedly upregulated at P0 in the CO pancreas: growth arrest specific 6 ( Show less
Glucose is an important inducer of insulin secretion, but it also stimulates long-term adaptive changes in gene expression that can either promote or antagonize the proliferative potential and functio Show more
Glucose is an important inducer of insulin secretion, but it also stimulates long-term adaptive changes in gene expression that can either promote or antagonize the proliferative potential and function of β cells. Here, we have generated time-resolved profiles of enhancer and transcriptional activity in response to glucose in the INS-1E pancreatic β cell line. Our data outline a biphasic response with a first transcriptional wave during which metabolic genes are activated, and a second wave where cell-cycle genes are activated and β cell identity genes are repressed. The glucose-sensing transcription factor ChREBP directly activates first wave enhancers, whereas repression and activation of second wave enhancers are indirect. By integrating motif enrichment within late-regulated enhancers with expression profiles of the associated transcription factors, we have identified multiple putative regulators of the second wave. These include RORγ, the activity of which is important for glucose-induced proliferation of both INS-1E and primary rat β cells. Show less