High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging
Summary: The glucagon receptor (GCGR) is a member of the class B G protein-coupled receptor family. Many research works have been carried out on GCGR structure, glucagon signaling pathway, and GCGR antagonists. However, the expression and fine distribution of GCGR proteins in response to glucagon un...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223000445 |
| _version_ | 1797903359418564608 |
|---|---|
| author | Jing Gao Hongru Li Haijiao Xu Yong Liu Mingjun Cai Yan Shi Jingrui Zhang Hongda Wang |
| author_facet | Jing Gao Hongru Li Haijiao Xu Yong Liu Mingjun Cai Yan Shi Jingrui Zhang Hongda Wang |
| author_sort | Jing Gao |
| collection | DOAJ |
| description | Summary: The glucagon receptor (GCGR) is a member of the class B G protein-coupled receptor family. Many research works have been carried out on GCGR structure, glucagon signaling pathway, and GCGR antagonists. However, the expression and fine distribution of GCGR proteins in response to glucagon under high glucose remain unclear. Using direct stochastic optical reconstruction microscopy (dSTORM) imaging, nanoscale GCGR clusters were observed on HepG2 cell membranes, and high glucose promoted GCGR expression and the formation of more and larger clusters. Moreover, glucagon stimulation under high glucose did not inhibit GCGR levels as significantly as that under low glucose and did not increase the downstream cyclic 3,5′-adenosine monophosphate-protein kinase A (cAMP-PKA) signal, and there were still large-size clusters on the membranes, indicating that high glucose induced glucagon resistance. In addition, high glucose induced stronger glucagon resistance in hepatoma cells compared with hepatic cells. Our work will pave a way to further our understanding of the pathogenesis of diabetes and develop more effective drugs targeting GCGR. |
| first_indexed | 2024-04-10T09:31:39Z |
| format | Article |
| id | doaj.art-1b53c36e23584412a1914344aad64714 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-10T09:31:39Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1b53c36e23584412a1914344aad647142023-02-19T04:26:45ZengElsevieriScience2589-00422023-02-01262105967High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imagingJing Gao0Hongru Li1Haijiao Xu2Yong Liu3Mingjun Cai4Yan Shi5Jingrui Zhang6Hongda Wang7State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, China; Corresponding authorState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, China; University of Science and Technology of China, Hefei, Anhui 230027, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Research Center of Biomembranomics, Changchun, Jilin 130022, China; University of Science and Technology of China, Hefei, Anhui 230027, China; Laboratory for Marine Biology and Biotechnology, Qing dao National Laboratory for Marine Science and Technology, Wenhai Road, Aoshanwei, Jimo, Qingdao, Shandong 266237, China; Corresponding authorSummary: The glucagon receptor (GCGR) is a member of the class B G protein-coupled receptor family. Many research works have been carried out on GCGR structure, glucagon signaling pathway, and GCGR antagonists. However, the expression and fine distribution of GCGR proteins in response to glucagon under high glucose remain unclear. Using direct stochastic optical reconstruction microscopy (dSTORM) imaging, nanoscale GCGR clusters were observed on HepG2 cell membranes, and high glucose promoted GCGR expression and the formation of more and larger clusters. Moreover, glucagon stimulation under high glucose did not inhibit GCGR levels as significantly as that under low glucose and did not increase the downstream cyclic 3,5′-adenosine monophosphate-protein kinase A (cAMP-PKA) signal, and there were still large-size clusters on the membranes, indicating that high glucose induced glucagon resistance. In addition, high glucose induced stronger glucagon resistance in hepatoma cells compared with hepatic cells. Our work will pave a way to further our understanding of the pathogenesis of diabetes and develop more effective drugs targeting GCGR.http://www.sciencedirect.com/science/article/pii/S2589004223000445Optical imagingBiological sciencesCell biology |
| spellingShingle | Jing Gao Hongru Li Haijiao Xu Yong Liu Mingjun Cai Yan Shi Jingrui Zhang Hongda Wang High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging iScience Optical imaging Biological sciences Cell biology |
| title | High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging |
| title_full | High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging |
| title_fullStr | High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging |
| title_full_unstemmed | High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging |
| title_short | High glucose-induced glucagon resistance and membrane distribution of GCGR revealed by super-resolution imaging |
| title_sort | high glucose induced glucagon resistance and membrane distribution of gcgr revealed by super resolution imaging |
| topic | Optical imaging Biological sciences Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223000445 |
| work_keys_str_mv | AT jinggao highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT hongruli highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT haijiaoxu highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT yongliu highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT mingjuncai highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT yanshi highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT jingruizhang highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging AT hongdawang highglucoseinducedglucagonresistanceandmembranedistributionofgcgrrevealedbysuperresolutionimaging |