Identification of a novel human glucagon receptor promoter: regulation by cAMP and PGC-1alpha.

Previously we have demonstrated that glucagon receptor mRNA expression in cultured rat hepatocytes and pancreatic islets can be regulated by various factors, including cAMP; however, the regulation of the human glucagon receptor gene has not been well-defined. Here we have characterized the promoter regions of the human glucagon receptor gene. Primer extension studies yielded multiple products in both liver and pancreas, corresponding to transcription start sites situated at -166 and -477 relative to the start of translation, indicating two putative promoters.

Gene delivery by an epidermal growth factor/DNA polyplex to small cell lung cancer cell lines expressing low levels of epidermal growth factor receptor.

In the present study, we wanted to determine whether efficient gene delivery using an epidermal growth factor (EGF)/DNA polyplex could be accomplished in small cell lung cancer (SCLC) cell lines expressing low EGF receptor (EGFR) levels. EGFR expression levels and transduction efficiencies with polyplexes were examined in five SCLC cell lines and two controls. EGFR expression was examined by binding assays and demonstrated low EGFR levels ranging from 3.

Gene therapy for lung cancer.

In the pre-clinical research into the development of gene therapy for cancer, different strategies have evolved and shown promising results in the laboratory. However, most of these strategies will need further refinement to obtain clinical success. This is partly due to the lack of suitable vector systems which specifically can deliver the therapeutic gene to the target cells, and ensure expression of the therapeutic gene.

Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines.

Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines.

The Gly40Ser mutation in the human glucagon receptor gene associated with NIDDM results in a receptor with reduced sensitivity to glucagon.

The pancreatic islet hormone, glucagon, stimulates hepatic glucose production and has also been shown to potentiate glucose-induced insulin secretion. Because glucagon is a key regulator of glucose homeostasis, its receptor, which mediates the actions of glucagon, was considered a candidate gene involved in the pathogenesis of NIDDM. We have previously reported that a single heterozygous missense mutation in exon 2 of the glucagon receptor gene, which changes a glycine to a serine (Gly40Ser), is associated with NIDDM in a French population.

Regulation of glucagon receptor mRNA in cultured primary rat hepatocytes by glucose and cAMP.

Glucagon, the pancreatic hormone secreted in response to hypoglycemia, is a key regulator of hepatic glucose production. Since the number of specific glucagon receptors expressed on the cell surface affects the sensitivity of the liver to glucagon, we have examined the regulation of glucagon receptor mRNA levels in cultured primary rat hepatocytes. By ribonuclease protection assay we have identified glucose and intracellular cAMP as regulators of glucagon receptor mRNA expression in cultured rat hepatocytes.

Regulation of glucagon and glucagon-like peptide-1 receptor messenger ribonucleic acid expression in cultured rat pancreatic islets by glucose, cyclic adenosine 3',5'-monophosphate, and glucocorticoids.

Glucagon and glucagon-like peptide-1 (GLP-1) are important regulators of glucose homeostasis, and both are involved in regulating pancreatic islet hormone secretion. Since the sensitivity of the endocrine pancreas to regulatory hormones can be influenced by their receptor number, we have examined the regulation of glucagon receptor and GLP-1 receptor messenger RNA (mRNA) expression in cultured rat pancreatic islets by various factors, including glucose, cAMP, and glucocorticoids. By ribonuclease protection assay we have demonstrated the expression of both glucagon and GLP-1 receptor mRNA in cultured rat islets.

Glucagon receptor mRNA distribution in rat tissues.

In addition to glucagon's role in regulating glucose production from the liver, a number of extrahepatic effects of glucagon have been reported. We have therefore examined various rat tissues for glucagon receptor mRNA expression. In liver, kidney, heart, adipose tissue, spleen, pancreatic islets, ovary, and thymus, glucagon receptor mRNA expression was found to be relatively abundant whereas lower levels were detected in stomach, small intestine, adrenal gland, thyroid, and skeletal muscle.

Cis-regulatory sequences leading to female-specific expression of yolk protein genes 1 and 2 in the fat body of Drosophila melanogaster.

The three yolk protein genes (yp) of Drosophila melanogaster are transcribed in a sex- and tissue-limited fashion. We have searched for cis-regulatory sequences in regions flanking yp1 and yp2 to identify the elements that confer female-specific expression in the fat body. One such 127 bp element has previously been identified in this region.

Do the pyramids show continental drift?

The mystery of the orientation of the Great Pyramids of Giza has remained unexplained for many decades. The general alignment is 4 minutes west of north. It is argued that this is not a builders' error but is caused by movement over the centuries.