Exendin-4 and exendin-(9–39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7–36)NH2

Schepp, Wolfgang; Schmidtler, J.; Riedel, Thomas; Dehne, Kerstin; Schusdziarra, V.; Holst, Jens J.; Eng, John; Raufman, Jean‐Pierre; Classen, Meinhard

doi:10.1016/0922-4106(94)90085-x

Cited by 55 publications

(29 citation statements)

References 19 publications

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“…Likewise, neither compound activated cells expressing receptors for glucagon or GLP-2, which, like GLP-1, are also processed from pro-glucagon in a tissuespecific manner. As with GLP-1, cellular effects of S4P and Boc5 were blocked with exendin(9-39), a ligand reported to be a selective antagonist of GLP-1R (16). Finally, dose-dependent insulinotropic effects were observed in isolated rat pancreatic islets, a system in which endogenous GLP-1 sensitivity was manifest.…”

Section: Discussionmentioning

confidence: 99%

A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db / db mice

Chen

Liao

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

157

143

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Section: Discussionmentioning

confidence: 99%

A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db / db mice

Chen

Liao

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

157

143

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“…Its function is not known for all these locations (see below). For instance, in the parietal cells, activation of the receptor increases aminopyrine accumulation, which is an indirect indicator of acid secretion (258), whereas in vivo, GLP-1 strongly inhibits acid secretion (see below). Numerous attempts have been made to identify alternative GLP-1 receptors or subtypes (see below), but at present only a single GLP-1 receptor has been identified, whether expressed in the brain, the stomach, or the pancreas (322).…”

Section: Effects Of Glucagon-like Peptide 1 a The Glp-1 Receptormentioning

confidence: 99%

The Physiology of Glucagon-like Peptide 1

Holst¹

2007

Physiological Reviews

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2,709

2,385

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Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the “ileal brake” mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.

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“…Exendin-4 is an insulinotropic glucagon-like peptide-1 agonist that associates with ␤-pancreatic cells, elevates endogenous cAMP levels, enhances secretion of insulin, and lowers circulating glucose levels (22)(23)(24)(25). A profound pharmacological advantage of this glucagon-like peptide-1 agonist is that (following administration at any dosage) the circulating blood glucose level never falls below a threshold that in non-diabetic healthy CD1 mice is 74 Ϯ 7 mg/dl (26).…”

Section: Demonstrating the Validity Of Reversible Pegylation With Hghmentioning

confidence: 99%

Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification

Tsubery

Mironchik²,

Fridkin

et al. 2004

Journal of Biological Chemistry

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Exendin-4 and exendin-(9–39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7–36)NH2

Cited by 55 publications

References 19 publications

A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db / db mice

A nonpeptidic agonist of glucagon-like peptide 1 receptors with efficacy in diabetic db / db mice

The Physiology of Glucagon-like Peptide 1

Prolonging the Action of Protein and Peptide Drugs by a Novel Approach of Reversible Polyethylene Glycol Modification

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