In the present study, we investigated whether cholecystokinin (CCK) or its structurally related peptide gastrin participates in long term regulation of adipocyte leptin secretion. The levels of circulating leptin observed after 2 and 6 h of refeeding in 18-h fast rats were significantly lowered by injection of the specific gastrin/CCK-B receptor antagonist YM022 at doses that did not affect feeding behavior. Moreover, in normally fed animals, circulating leptin was markedly decreased by chronic injection of YM022 (from 4 +/- 0.6 to 2.1 +/- 0.5 ng/ml). Consistent with these observations, YM022 treatment decreased leptin messenger RNA (mRNA) levels and increased the leptin content in rat epididymal fat tissue. Rat adipocytes exclusively contain gastrin/CCK-B receptor mRNA, but not CCK-A receptor mRNA. Furthermore, adipocyte membranes bound [125I]CCK-8 in a saturable manner, with kinetics consistent with a single class of high affinity sites with a Kd of 0.2 nM. These data argue for a physiological role for the CCK-B/gastrin receptor in adipocyte leptin regulation. We therefore propose that gastrin is involved in long term regulation of leptin expression and secretion in rat fat tissues through activation of an adipocyte gastrin/CCK-B receptor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1210/endo.140.10.7079 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Gastrin/CCK-B Receptor Signaling Promotes Cell Invasion and Metastasis by Upregulating MMP-2 and VEGF Expression in Gastric Cancer.
J Cancer
January 2022
Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education and Key Laboratory of Medical Molecular Biology, Guizhou Medical University, Guiyang, Guizhou, China.
Accumulated evidence suggests that a functional loop composed of gastrin and cholecystokinin B receptor (CCK-BR) may exist in gastric carcinogenesis. However, this suggestion is not completely supported due to a lack of direct evidence, and the underlying mechanism is not completely understood. Here, we evaluated the effects of gastrin/CCK-BR signaling on the cell growth, invasion, and expression of MMP-2 and VEGF, as well as xenograft growth .
View Article and Find Full Text PDFOrganocatalytic Enantioselective Mukaiyama-Mannich Reaction of Isatin-Derived Ketimines for the Synthesis of Oxindolyl-β -Amino Acid Esters.
Chemistry
November 2019
Centre of Biomedical Research, Sanjay Gandhi Post-Graduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow, 226014, India.
Mukaiyama-Mannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of β-amino acids; nevertheless, the corresponding asymmetric reaction employing ketimines are unexplored. Herein, the first organocatalytic enantioselective Mukaiyama-Mannich reaction employing isatin-derived ketimines with unsubstituted silyl ketene acetals is disclosed towards the scalable synthesis of 2-oxoindolinyl-β -amino acid esters at room temperature with excellent enantioselectivities (ee >99.5 %).
View Article and Find Full Text PDFGastrin and Gastric Cancer.
Cell Mol Gastroenterol Hepatol
July 2017
Cato Research, Durham, North Carolina.
Gastric cancer is the third leading cause of cancer-related mortality worldwide. Despite progress in understanding its development, challenges with treatment remain. Gastrin, a peptide hormone, is trophic for normal gastrointestinal epithelium.
View Article and Find Full Text PDFThe uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients.
Scand J Gastroenterol
October 2016
c Department of Surgical Gastroenterology, Rigshospitalet , University of Copenhagen, Copenhagen , Denmark ;
Objective: Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma syndrome in man has remained unknown until now.
View Article and Find Full Text PDFA highly efficient Mukaiyama-Mannich reaction of N-Boc isatin ketimines and other active cyclic ketimines using difluoroenol silyl ethers catalyzed by Ph3PAuOTf.
Org Biomol Chem
December 2015
Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663N, Zhongshan Road, Shanghai 200062, China.
Ph3PAuOTf is identified as a powerful catalyst for the addition of difluoroenol silyl ethers to N-Boc isatin ketimines and other two kinds of active cyclic ketimines. This represents the first Au(i)-catalyzed Mukaiyama-Mannich reaction, and the corresponding non-fluorinated enol silyl ether proves to be even much more reactive under the same conditions. This method paves the way to the total synthesis of difluoromethylated analogues of AG-041R, a gastrin/CCK-B receptor antagonist.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!