The global transcriptional response of isolated human islets of langerhans to glucagon-like Peptide-1 receptor agonist liraglutide.

GLP-1 and its analog have been used in diabetes treatment; however, the direct alteration of gene expression profile in human islets induced by GLP-1 has not been reported. In present study, transcriptional gene expression in the liraglutide-treated human islets was analyzed with 12 human U133A chips including 23000 probe sets. The data compared between liraglutide and control groups showed a significant difference on glucose-induced insulin secretion, rather than viability.

Glucagon like peptide-1-directed human embryonic stem cells differentiation into insulin-producing cells via hedgehog, cAMP, and PI3K pathways.

Objectives: That glucagonlike peptide-1 (GLP-1) induces differentiation of primate embryonic stem (ES) cells into insulin-producing cells has been reported by several groups and also confirmed with our observations.

Methods: To further elucidate the process in detail and the signaling pathways involved in this differentiation, we induced human ES cells HUES1 differentiated into insulin secretion cells by GLP-1 treatment.

Results: A time-dependent pattern of down expression of the stem cell markers (human telomerase reverse transcriptase and octamer-4), and the appearance of multiple beta-cell-specific proteins (insulin, glucokinase, glucose transporter, type 2, and islet duodenal homeobox 1) and hedgehog signal molecules (Indian hedgehog, sonic hedgehog, and hedgehog receptor, patched) have been identified.

MyD88 and TRIF mediate the cyclic adenosine monophosphate (cAMP) induced corticotropin releasing hormone (CRH) expression in JEG3 choriocarcinoma cell line.

Background: Classically protein kinase A (PKA) and transcription factor activator protein 1 (AP-1) mediate the cyclic AMP (cAMP) induced-corticotrophin releasing hormone (CRH) expression in the placenta. However enteric Gram (-) bacterial cell wall component lipopolysaccharide (LPS) may also induce-CRH expression via Toll like receptor (TLR)4 and its adaptor molecule Myd88. Here we investigated the role of MyD88, TRIF and IRAK2 on cAMP-induced CRH promoter activation in JEG3 cells in the absence of LPS/TLR4 stimulation.

Pancreatic beta-cells expressing GLP-1 are resistant to the toxic effects of immunosuppressive drugs.

Glucose intolerance is often observed after pancreatic islet cell transplantation. The administration of immunosuppressive agents (ISD), necessary to avoid tissue rejection, is in part responsible for hyperglycemia. To investigate whether mouse insulinoma (MIN6) cells transfected with the glucagon like peptide-1 (GLP-1) fragment of the proglucagon gene (RIP/GLP-1 MIN6 cells) are resistant to the toxicity derived from the administration of ISD.

Adenovirus-mediated XIAP gene transfer reverses the negative effects of immunosuppressive drugs on insulin secretion and cell viability of isolated human islets.

Immunosuppressive drugs are routinely used to provide tolerance after whole pancreas and islet cell transplantations. While they are essential in inhibiting graft rejection, little is known about their effect on islet function and beta-cell viability. In this study, we report that tacrolimus, sirolimus, and mycophenolic acid, when added to cultures of freshly isolated human islets, induce a downregulation of the synthesis and secretion of insulin.

Glucagon-like peptide 1 inhibits cell apoptosis and improves glucose responsiveness of freshly isolated human islets.

The peptide hormone, glucagon-like peptide 1 (GLP-1), has been shown to increase glucose-dependent insulin secretion, enhance insulin gene transcription, expand islet cell mass, and inhibit beta-cell apoptosis in animal models of diabetes. The aim of the present study was to evaluate whether GLP-1 could improve function and inhibit apoptosis in freshly isolated human islets. Human islets were cultured for 5 d in the presence, or absence, of GLP-1 (10 nm, added every 12 h) and studied for viability and expression of proapoptotic (caspase-3) and antiapoptotic factors (bcl-2) as well as glucose-dependent insulin production.

Insulin and glucose regulate the expression of the DNA repair enzyme XPD.

Nucleotide excision repair (NER) of damaged DNA is operated by a complex network of DNA repair enzymes that include a protein termed xeroderma pigmentosum complementation group D (XPD). We have previously reported that the expression of XPD is regulated by activation of the insulin receptor and that mutations of the tyrosine kinase domain of the receptor inhibit the insulin-dependent increase in XPD messenger RNA (mRNA) and protein levels. In the present study, we characterize the insulin-dependent signaling pathway leading to the control of XPD expression.