UM  > Institute of Chinese Medical Sciences
Affiliated with RCfalse
Status已發表Published
Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets
Pradhan, Geetali1,2; Lee, Jong Han1,3; Wu, Chia Shan4; Wang, Hongying4; Lin, Ligen1,5; Donti, Taraka6,7; Graham, Brett H.6,8; Rajan, Arun S.9; Balasubramanyam, Ashok9; Samson, Susan L.9; Guo, Shaodong4; Sun, Yuxiang1,4
2022-03-01
Source PublicationBiomolecules
ISSN2218-273X
Volume12Issue:3
Abstract

Ghrelin receptor, a growth hormone secretagogue receptor (GHS-R), is expressed in the pancreas. Emerging evidence indicates that GHS-R is involved in the regulation of glucose-stimulated insulin secretion (GSIS), but the mechanism by which GHS-R regulates GSIS in the pancreas is unclear. In this study, we investigated the role of GHS-R on GSIS in detail using global Ghsr mice (in vivo) and Ghsr-ablated pancreatic islets (ex vivo). GSIS was attenuated in both Ghsr mice and Ghsr-ablated islets, while the islet morphology was similar between WT and Ghsr mice. To elucidate the mechanism underpinning Ghsr-mediated GSIS, we investigated the key steps of the GSIS signaling cascade. The gene expression of glucose transporter 2 (Glut2) and the glucose-metabolic intermediate—glucose-6-phosphate (G6P) were reduced in Ghsr-ablated islets, supporting decreased glucose uptake. There was no difference in mitochondrial DNA content in the islets of WT and Ghsr mice, but the ATP/ADP ratio in Ghsr islets was significantly lower than that of WT islets. Moreover, the expression of pancreatic and duodenal homeobox 1 (Pdx1), as well as insulin signaling genes of insulin receptor (IR) and insulin receptor substrates 1 and 2 (IRS1/IRS2), was downregulated in Ghsr islets. Akt is the key mediator of the insulin signaling cascade. Concurrently, Akt phosphorylation was reduced in the pancreas of Ghsr mice under both insulin-stimulated and homeostatic conditions. These findings demonstrate that GHS-R ablation affects key components of the insulin signaling pathway in the pancreas, suggesting the existence of a cross-talk between GHS-R and the insulin signaling pathway in pancreatic islets, and GHS-R likely regulates GSIS via the Akt-Pdx1-GLUT2 pathway.

KeywordGlucose Transporter 2 (Glut2) Glucose-stimulated Insulin Secretion (Gsis) Growth Hormone Secretagogue Receptor (Ghs-r) Insulin Islets Pancreatic And Duodenal Homeobox 1 (Pdx1)
DOI10.3390/biom12030407
URLView the original
Language英語English
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000776849300001
Scopus ID2-s2.0-85126010553
Fulltext Access
Citation statistics
Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSun, Yuxiang
Affiliation1.USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, 77030, United States
2.Baylor College of Medicine, Houston, 77030, United States
3.Department of Marine Bioindustry, Hanseo University, Seosan, 31962, South Korea
4.Department of Nutrition, Texas A&M University, College Station, 77843, United States
5.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, 999078, Macao
6.Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, United States
7.PerkinElmer Genomics, Pittsburgh, 250 Industry Dr, 15275, United States
8.Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, 46202, United States
9.Department of Medicine, Baylor College of Medicine, Houston, 77030, United States
Recommended Citation
GB/T 7714
Pradhan, Geetali,Lee, Jong Han,Wu, Chia Shan,et al. Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets[J]. Biomolecules,2022,12(3).
APA Pradhan, Geetali,Lee, Jong Han,Wu, Chia Shan,Wang, Hongying,Lin, Ligen,Donti, Taraka,Graham, Brett H.,Rajan, Arun S.,Balasubramanyam, Ashok,Samson, Susan L.,Guo, Shaodong,&Sun, Yuxiang.(2022).Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets.Biomolecules,12(3).
MLA Pradhan, Geetali,et al."Mechanistic Investigation of GHS-R Mediated Glucose-Stimulated Insulin Secretion in Pancreatic Islets".Biomolecules 12.3(2022).
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Pradhan, Geetali]'s Articles
[Lee, Jong Han]'s Articles
[Wu, Chia Shan]'s Articles
Baidu academic
Similar articles in Baidu academic
[Pradhan, Geetali]'s Articles
[Lee, Jong Han]'s Articles
[Wu, Chia Shan]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Pradhan, Geetali]'s Articles
[Lee, Jong Han]'s Articles
[Wu, Chia Shan]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.