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GLP-1 and GLP-2 exhibit a diverse array of metabolic, proliferative and cytoprotective actions with important clinical implications for the treatment of diabetes and gastrointestinal disease--REVIEW GLP-1 and GLP-2 exhibit a diverse array of metabolic, proliferative and cytoprotective actions with important clinical implications for the treatment of diabetes and gastrointestinal disease--REVIEW. GLP-1 has to be present in blood to stimulate insluin or suppress glucagon. Human pancreatic beta cells do not appear to possess memory for insulinotropic stimuli. GLP-1 improves function and inhibit apoptosis in freshly isolated human islets. GLP-1 is preserved in type 2 diabetic patients, this peptide was a candidate as a therapeutic agent for this disease. (review). GLP-1 may be another important determiner of pancreatic endocrine differentiation as is pdx-1. GLP-1 protects against myocardial infarction in the isolated and intact rat heart. GLP-1, like insulin, stimulates glucose uptake in myocytes, and this involves activation of PI3K/PKB, p44/42 MAPKs, partially p70s6k, and possibly PKC. GLP-2 may prove to be important in the attempt to optimize remnant intestinal function thereby eliminating the need for parenteral support in short bowel syndrome. Glucagon inhibits ghrelin secretion in humans. In morbid obesity, accelerated inactivation of circulating GLP-1 could at least partially account for plasma peptide levels lower than normal, defective availability of such a satiety factor possibly contributing to eating behaviour abnormalities. Increased GLP-1 levels, which lead to decreased food intake, may also contribute to the weight loss that is associated with the use of this drug in obese diabetics. Reduced secretion or action of GLP-1 or GIP does not explain a relative reduced beta-cell responsiveness to glucose or the slightly elevated plasma glucose concentrations observed in young low birth weight men. Results demonstrate that glucagon like peptide-1 is capable of preserving beta-cell function and protecting cells from apoptotic cell death. Review article focuses on the complex integrative mechanisms that regulate the secretion of GLP-1 and GLP-2 from intestinal L cells, including both direct and indirect regulation by ingested nutrients. The glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1. The isolated N-terminal domain of the glucagon-like peptide-1 (GLP-1) receptor binds exendin peptides with much higher affinity than GLP-1. The protein encoded by this gene is actually a preproprotein that is cleaved into four distinct mature peptides. One of these, glucagon, is a pancreatic hormone that counteracts the glucose-lowering action of insulin by stimulating glycogenolysis and gluconeogenesis. Glucagon is a ligand for a specific G-protein linked receptor whose signalling pathway controls cell proliferation. Two of the other peptides are secreted from gut endocrine cells and promote nutrient absorption through distinct mechanisms. Finally, the fourth peptide is similar to glicentin, an active enteroglucagon. There are interactions between this protein, specific NEFA and insulin secretion. Conclude that the elimination of GLP-1 is the same in obese type 2 diabetic petients and matched healthy subjects. Delayed elimination in renal insufficiency. Glicentin plays an important role in the regulating inhibition of the contraction reaction in normal human jejunum via NANC nerves, and has a direct action on the jejunal muscle receptor. Important role for the irregularities in glucagon response in the postprandial glucose excursion in glucose intolerance and type 2 diabetes. In overweight/obese subjects, glucagon-like peptide 1 concentrations after weight loss were decreased compared with before weight loss, and nutrient-related stimulation was abolished. Leptin stimulates GLP-1 secretion from rodent and human intestinal L cells; leptin resistance may account for the decreased levels of GLP-1 found in obese humans. Low secretion of GLP-1 in girls with obesity may seriously and negatively influence the course of this disease while low levels in girls with anorexia nervosa are beneficial and promote appetite. Present in human colorectal adenocarcinomas and liver metastases. Role of M1 and M2 muscarinic receptors expressed by human L cells in the control of GLP-1 secretion. Role of polarity at Asp198 in determining binding site for glucagon-like peptide-1 receptor. Single treatment of sensitized mice with GLP diminishes both immediate and late-phase hypersensitivity reactions characteristic of food allergy by inhibiting transepithelial uptake of antigen. Some of the events that lead to the differentiation of pancreatic ductal cells in response to treatment with human GLP-1.
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