Background & Aims: Glucagon-like peptide (GLP)-2, a product of the proglucagon gene, is expressed in enteroendocrine cells of the small and large intestine and is trophic to the gastrointestinal mucosa. GLP-2 also inhibits gastric acid secretion and emptying and up-regulates intestinal hexose transport. GLP-2 acts via binding to a single G protein-coupled GLP-2 receptor (GLP-2R), but the cellular targets for the diverse actions of GLP-2 remain unknown.
Methods: GLP-2R expression in rodent and human tissues was examined using a combination of Northern blotting, reverse-transcription polymerase chain reaction (RT-PCR), and immunocytochemistry.
Results: A single major GLP-2R messenger RNA transcript was detected by Northern blot analysis in rodent stomach, duodenum, jejunum, ileum, and colon, but not in rodent esophagus. GLP-2R expression was also detected by RT-PCR in RNA from the hypothalamus, brain stem, and lung. Immunocytochemical localization of human GLP-2R expression using specific antisera detected GLP-2R immunopositivity in subsets of endocrine cell populations in the epithelium of the stomach and both the small and large bowel.
Conclusions: These findings suggest that enteroendocrine-derived GLP-2 acts directly on endocrine cells to induce one or more downstream mediators of GLP-2 action in the gastrointestinal tract.
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http://dx.doi.org/10.1053/gast.2000.16489 | DOI Listing |
ACS Cent Sci
May 2024
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Peptides
July 2024
Center for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark. Electronic address:
Recent advancements in understanding glucagon-like peptide 2 (GLP-2) biology and pharmacology have sparked interest in targeting the GLP-2 receptor (GLP-2R) in the treatment of obesity. GLP-2 is a proglucagon-derived 33-amino acid peptide co-secreted from enteroendocrine L cells along with glucagon-like peptide 1 (GLP-1) and has a range of actions via the GLP-2R, which is particularly expressed in the gastrointestinal tract, the liver, adipose tissue, and the central nervous system (CNS). In humans, GLP-2 evidently induces intestinotrophic effects (i.
View Article and Find Full Text PDFJ Med Chem
August 2023
Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada.
Here, we designed three d-GLP-2 agonists that activated the glucagon-like peptide-2 receptor (GLP-2R) cyclic adenosine monophosphate (cAMP) accumulation without stimulating the glucagon-like peptide-1 receptor (GLP-1R). All the d-GLP-2 agonists increased the protein kinase B phosphorylated (p-AKT) expression levels in a time- and concentration-dependent manner in vitro. The most effective d-GLP-2 analogue boosted the AKT phosphorylation 2.
View Article and Find Full Text PDFJ Alzheimers Dis Rep
November 2022
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
Background: Glucagon-like peptide-2 (GLP-2) is an intestinal trophic factor that induces astrocyte proliferation through its own receptor (GLP-2R), but the control of its expression is not well known.
Objective: To study the effects of glucose and of different mitogenic agents on the control of GLP-2R expression in cultured rat astrocytes.
Methods: GLP-2R mRNA content was measured by quantitative RT-PCR.
Pharmacol Rep
October 2022
Department of Biochemical Toxicology, Chair of Toxicology, Medical College, Jagiellonian University, Medyczna 9, 30-688, Kraków, Poland.
Metabolic disturbances in the brain are assumed to be early changes involved in the pathogenesis of depression, and these alterations may be intensified by a deficiency of thyroid hormones. In contrast to glucose metabolism, the link between altered brain lipids and the pathogenesis of depression is poorly understood, therefore in the present study, we determine transcription factors and enzymes regulating cholesterol and fatty acid biosynthesis in the brain structures in an animal model of depression, hypothyroidism and the coexistence of these diseases.In used model of depression, a decrease in the active form of the transcription factor SREBP-2 in the hippocampus was demonstrated, thus suggesting a reduction in cholesterol biosynthesis.
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