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Our data demonstrate that H pylori infection promotes gastric epithelial cells invasion by activating MMP-9 and VEGF expression. These effects appear to be mediated through a NF-kappaB and COX-2 mediated pathway, as COX-2 or NF-kappaB inhibitor significantly attenuate the invasiveness of gastric cancer cells and the expressions of MMP-9 and VEGF protein.

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are potent insulinotropic peptides released from the small intestine. To examine their relative contribution to postprandial insulin release, a specific GIP antagonist (ANTGIP) and a GLP-1 antagonist, exendin-(9—39)-NH2, were infused into rats after an intragastric glucose meal. In control rats, plasma glucose and insulin levels rose gradually during the first 20 min and then decreased. Exendin-(9—39)-NH2 administration inhibited postprandial insulin secretion by 32% at 20 min and concomitantly increased plasma glucose concentrations. In contrast, ANTGIP treatment not only induced a 54% decrease in insulin secretion but also a 15% reduction in plasma glucose levels 20 min after the glucose meal. In vivo studies in rats demonstrated that glucose uptake in the upper small intestine was significantly inhibited by the ANTGIP, an effect that might account for the decrease in plasma glucose levels observed in ANTGIP-treated rats. When the two antagonists were administered to rats concomitantly, no potentiating effect on either insulin release or plasma glucose concentration was detected. Glucose meal-stimulated GLP-1 release was not affected by ANTGIP administration, whereas postprandial glucagon levels were diminished in rats receiving exendin-(9—39)-NH2. The results of these studies suggest that GIP and GLP-1 may share a common mechanism in stimulating pancreatic insulin release. Furthermore, the GIP receptor appears to play a role in facilitating glucose uptake in the small intestine.

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that stimulates insulin secretion from pancreatic beta cells in the presence of glucose. Approximately 7.8 x 105 recombinant dones of a neonatal rat intestinal cDNA library were screened by using plaque hybridization, and three dones were identified and sequenced with the dideoxynucleotide chain-termination method. The translated amino acid sequence deduced from the nucleotide sequence of the cDNA indicated that rat GIP was derived by proteolytic processing of a 144-amino acid precursor polypeptide. The mature peptide is flanked by a 43-amino acid NH2-terminal peptide that contains a 21-amino add signal peptide and by a 59-amino acid COOH-terminal peptide. Analysis of the nucleotide and amino acid sequence of rat GIP revealed only two substitutions from the known human GIP peptide. The use of high-stringency RNA blot-hybridization analysis of total RNA extracted from various organs demonstrated expression of the GIP gene in the duodenum and jejunum and, to a lesser extent, in the ileum. In addition, expression of the GIP gene was observed in the submandibular salivary gland both by RNA analysis and RIA. In response to duodenal perfusion of a 20% Lipomul meal for 60 min, duodenal mucosal GIP mRNA concentrations increased by 42.8% and 48.2% at 30 and 60 min, respectively.Glucose-dependent insulinotropic peptide (GIP) was first isolated from porcine small intestine in 1969 and was originally named "gastric inhibitory peptide" on the basis of its ability to inhibit acid secretion in dogs (1). Its primary structure was initially described in 1971 (2) and revised in 1981 (3), and its amino acid sequence placed it in the secretin family of gastrointestinal regulatory peptides. GIP has been demonstrated in the cytoplasmic granules ofenteroendocrine K-cells in mucosa throughout the small intestine (4). After intestinal glucose perfusion, the primary site of endogenous GIP release appears to be the duodenum and proximal jejunum (5). Although several studies have supported the role of GIP as an inhibitor of acid secretion (6-10), some have challenged the notion that GIP inhibits acid output under physiological conditions (11,12). In addition to its inhibitory effects in the stomach, further investigation of the physiological properties of GIP demonstrated that in the presence of glucose, GIP enhanced insulin release by pancreatic beta islet cells when administered in physiological doses (13)(14)(15). It was, therefore, suggested that GIP may function as an "incretin," a proposed enteric factor that stimulates the release of pancreatic insulin and that may play a physiological role in maintaining glucose homeostasis (16,17). Accordingly, the hormone is now often referred to as "glucose-dependent insulinotropic peptide," thereby maintaining the original acronym (18).Numerous past studies have characterized GIP release into the circulation; however, few have examined the biosynthesis of this peptide. The rat serves as...