Inside the Insulin Secretory Granule
The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-08-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/11/8/515 |
| _version_ | 1797522913826439168 |
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| author | Mark Germanos Andy Gao Matthew Taper Belinda Yau Melkam A. Kebede |
| author_facet | Mark Germanos Andy Gao Matthew Taper Belinda Yau Melkam A. Kebede |
| author_sort | Mark Germanos |
| collection | DOAJ |
| description | The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the <i>trans</i>-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis. |
| first_indexed | 2024-03-10T08:36:04Z |
| format | Article |
| id | doaj.art-5014ae975e1449f29e091478b50ecb3f |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T08:36:04Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-5014ae975e1449f29e091478b50ecb3f2023-11-22T08:39:26ZengMDPI AGMetabolites2218-19892021-08-0111851510.3390/metabo11080515Inside the Insulin Secretory GranuleMark Germanos0Andy Gao1Matthew Taper2Belinda Yau3Melkam A. Kebede4School of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney 2006, AustraliaSchool of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney 2006, AustraliaSchool of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney 2006, AustraliaSchool of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney 2006, AustraliaSchool of Medical Sciences, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, Sydney 2006, AustraliaThe pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the <i>trans</i>-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis.https://www.mdpi.com/2218-1989/11/8/515insulinislet amyloid polypeptide (IAPP)graninsecretory pathwaytrans-Golgi network (TGN)granule |
| spellingShingle | Mark Germanos Andy Gao Matthew Taper Belinda Yau Melkam A. Kebede Inside the Insulin Secretory Granule Metabolites insulin islet amyloid polypeptide (IAPP) granin secretory pathway trans-Golgi network (TGN) granule |
| title | Inside the Insulin Secretory Granule |
| title_full | Inside the Insulin Secretory Granule |
| title_fullStr | Inside the Insulin Secretory Granule |
| title_full_unstemmed | Inside the Insulin Secretory Granule |
| title_short | Inside the Insulin Secretory Granule |
| title_sort | inside the insulin secretory granule |
| topic | insulin islet amyloid polypeptide (IAPP) granin secretory pathway trans-Golgi network (TGN) granule |
| url | https://www.mdpi.com/2218-1989/11/8/515 |
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