Heterogenous glucose-stimulated insulin secretion at single islet level
Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy m...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-12-01
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| Series: | Engineered Regeneration |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666138123000452 |
| _version_ | 1797628928112721920 |
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| author | Jiaxiang Yin Hao Meng Haopeng Lin Meijun Mo Jingfang Lin Jingyi Chen Lihua Chen Xiaojun Xu Zonghong Li Wei Ji Tao Xu Huisheng Liu |
| author_facet | Jiaxiang Yin Hao Meng Haopeng Lin Meijun Mo Jingfang Lin Jingyi Chen Lihua Chen Xiaojun Xu Zonghong Li Wei Ji Tao Xu Huisheng Liu |
| author_sort | Jiaxiang Yin |
| collection | DOAJ |
| description | Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level. |
| first_indexed | 2024-03-11T10:46:07Z |
| format | Article |
| id | doaj.art-8e1623826a004832aa46f728b72bbf54 |
| institution | Directory Open Access Journal |
| issn | 2666-1381 |
| language | English |
| last_indexed | 2024-03-11T10:46:07Z |
| publishDate | 2023-12-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Engineered Regeneration |
| spelling | doaj.art-8e1623826a004832aa46f728b72bbf542023-11-14T04:02:10ZengKeAi Communications Co., Ltd.Engineered Regeneration2666-13812023-12-0144387395Heterogenous glucose-stimulated insulin secretion at single islet levelJiaxiang Yin0Hao Meng1Haopeng Lin2Meijun Mo3Jingfang Lin4Jingyi Chen5Lihua Chen6Xiaojun Xu7Zonghong Li8Wei Ji9Tao Xu10Huisheng Liu11School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, Guangdong, China; Bioland Laboratory, Guangzhou, Guangdong, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaGuangzhou National Laboratory, Guangzhou, Guangdong, ChinaGuangzhou National Laboratory, Guangzhou, Guangdong, ChinaBioland Laboratory, Guangzhou, Guangdong, ChinaGuangzhou National Laboratory, Guangzhou, Guangdong, China; School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, Guangdong, ChinaGuangzhou National Laboratory, Guangzhou, Guangdong, ChinaGuangzhou National Laboratory, Guangzhou, Guangdong, ChinaBioland Laboratory, Guangzhou, Guangdong, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, ChinaSchool of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, Guangdong, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China; Corresponding authors.School of Biomedical Engineering, Guangzhou Medical University, Guangzhou, China; Guangzhou National Laboratory, Guangzhou, Guangdong, China; Bioland Laboratory, Guangzhou, Guangdong, China; Corresponding authors.Insulin secretion by pancreatic islets plays a vital role in regulating blood glucose levels. Nevertheless, the mechanism responsible for this dynamic insulin secretion has not been completely understood, particularly at the single islet level. In this study, we have successfully developed an easy microfluidic platform that allows for the exploration of dynamic glucose-stimulated insulin secretion (GSIS) at the single islet level. With the utilization of this platform, we evaluated dynamic GSIS from single islets isolated from both normal and diabetic rats. Our results demonstrate that islets can be categorized into three types based on their dynamic GSIS: Type I exhibits a biphasic GSIS profile with a fast first phase and flat second phase; Type II also has a biphasic GSIS profile with a fast first phase but a slow increased second phase; Type III displays only a slowly increased second phase and lacks a fast first phase. RNA sequencing analysis demonstrated that the cell type and exocytosis-specific genes are consistent with the proportion of cells and insulin release kinetics among the three types of islets, respectively. Moreover, our findings suggest that high expression of Atp5pb is anti-correlated with the first phase of insulin secretion. Furthermore, we revealed that diabetic islets exhibit only the type I GSIS response, indicating a deliberate impairment of the second phase of insulin secretion. Together, this device serves as a crucial tool in the research field of islets and diabetes, allowing researchers to investigate islet functional heterogeneity and identity at the single islet level.http://www.sciencedirect.com/science/article/pii/S2666138123000452Islet-on-a-chipSingle isletGlucose-stimulated insulin secretionHeterogeneityDiabetes |
| spellingShingle | Jiaxiang Yin Hao Meng Haopeng Lin Meijun Mo Jingfang Lin Jingyi Chen Lihua Chen Xiaojun Xu Zonghong Li Wei Ji Tao Xu Huisheng Liu Heterogenous glucose-stimulated insulin secretion at single islet level Engineered Regeneration Islet-on-a-chip Single islet Glucose-stimulated insulin secretion Heterogeneity Diabetes |
| title | Heterogenous glucose-stimulated insulin secretion at single islet level |
| title_full | Heterogenous glucose-stimulated insulin secretion at single islet level |
| title_fullStr | Heterogenous glucose-stimulated insulin secretion at single islet level |
| title_full_unstemmed | Heterogenous glucose-stimulated insulin secretion at single islet level |
| title_short | Heterogenous glucose-stimulated insulin secretion at single islet level |
| title_sort | heterogenous glucose stimulated insulin secretion at single islet level |
| topic | Islet-on-a-chip Single islet Glucose-stimulated insulin secretion Heterogeneity Diabetes |
| url | http://www.sciencedirect.com/science/article/pii/S2666138123000452 |
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