Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes
Summary: In type 2 diabetes (T2D), the rate of insulin secretory granule biogenesis can limit insulin secretion from pancreatic β-cells. Using rat insulinoma INS1 β-cells, we show that the soluble Ca2+-binding/trafficking protein, Cab45G, serves as a non-essential chaperone for insulin granule bioge...
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Elsevier
2025-02-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224029468 |
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| author | Mark Germanos Belinda Yau Matthew Taper Cara Yeoman Amy Wilson Yousun An Jerome Cattin-Ortolá Drew Masler Jason Tong Sheyda Naghiloo Elise J Needham A Gabrielle van der Kraan Kitty Sun Thomas Loudovaris Alexis Diaz-Vegas Mark Larance Helen Thomas Helen von Blume Peter Thorn Michael Ailion Cedric Asensio Melkam Alamerew Kebede |
| author_facet | Mark Germanos Belinda Yau Matthew Taper Cara Yeoman Amy Wilson Yousun An Jerome Cattin-Ortolá Drew Masler Jason Tong Sheyda Naghiloo Elise J Needham A Gabrielle van der Kraan Kitty Sun Thomas Loudovaris Alexis Diaz-Vegas Mark Larance Helen Thomas Helen von Blume Peter Thorn Michael Ailion Cedric Asensio Melkam Alamerew Kebede |
| author_sort | Mark Germanos |
| collection | DOAJ |
| description | Summary: In type 2 diabetes (T2D), the rate of insulin secretory granule biogenesis can limit insulin secretion from pancreatic β-cells. Using rat insulinoma INS1 β-cells, we show that the soluble Ca2+-binding/trafficking protein, Cab45G, serves as a non-essential chaperone for insulin granule biogenesis. In β-cells, Cab45G is stored within a cis-Golgi reservoir. Cab45G deletion dysregulates Ca2+ homeostasis and leads to secretory abnormality, but insulin granule biogenesis remains intact. Increasing Cab45G biosynthesis leads to anterograde trafficking into insulin granules, stimulating their production. Using human donor islets, we identify increased anterograde Cab45G trafficking in obese humans with and without T2D, consistent with the heightened demand for granule biogenesis. However, humans with T2D demonstrate decreased Golgi Cab45G localization and increased granule Cab45G localization compared to those without T2D. Our study provides the first insight into Cab45G function in specialized secretory cells and opens avenues of investigation into mechanisms associated with β-cell compensation and failure. |
| format | Article |
| id | doaj-art-0b8d04e39774468283347b526e29ff92 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-0b8d04e39774468283347b526e29ff922025-01-19T06:26:29ZengElsevieriScience2589-00422025-02-01282111719Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetesMark Germanos0Belinda Yau1Matthew Taper2Cara Yeoman3Amy Wilson4Yousun An5Jerome Cattin-Ortolá6Drew Masler7Jason Tong8Sheyda Naghiloo9Elise J Needham10A Gabrielle van der Kraan11Kitty Sun12Thomas Loudovaris13Alexis Diaz-Vegas14Mark Larance15Helen Thomas16Helen von Blume17Peter Thorn18Michael Ailion19Cedric Asensio20Melkam Alamerew Kebede21School of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaDepartment of Biochemistry, University of Washington, Seattle, WA, USADepartment of Biological Sciences, University of Denver, Denver, CO 80210, USASchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaImmunology and Diabetes Unit, St Vincent’s Institute, Department of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy, VIC 3065, AustraliaSchool of Life and Environmental Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaSchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaImmunology and Diabetes Unit, St Vincent’s Institute, Department of Medicine, St Vincent’s Hospital, University of Melbourne, Fitzroy, VIC 3065, AustraliaDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT 06510, USASchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaDepartment of Biochemistry, University of Washington, Seattle, WA, USADepartment of Biological Sciences, University of Denver, Denver, CO 80210, USASchool of Medical Sciences, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia; Corresponding authorSummary: In type 2 diabetes (T2D), the rate of insulin secretory granule biogenesis can limit insulin secretion from pancreatic β-cells. Using rat insulinoma INS1 β-cells, we show that the soluble Ca2+-binding/trafficking protein, Cab45G, serves as a non-essential chaperone for insulin granule biogenesis. In β-cells, Cab45G is stored within a cis-Golgi reservoir. Cab45G deletion dysregulates Ca2+ homeostasis and leads to secretory abnormality, but insulin granule biogenesis remains intact. Increasing Cab45G biosynthesis leads to anterograde trafficking into insulin granules, stimulating their production. Using human donor islets, we identify increased anterograde Cab45G trafficking in obese humans with and without T2D, consistent with the heightened demand for granule biogenesis. However, humans with T2D demonstrate decreased Golgi Cab45G localization and increased granule Cab45G localization compared to those without T2D. Our study provides the first insight into Cab45G function in specialized secretory cells and opens avenues of investigation into mechanisms associated with β-cell compensation and failure.http://www.sciencedirect.com/science/article/pii/S2589004224029468Biological sciencesCell biologyOrganizational aspects of cell biologySpecialized functions of cellsFunctional aspects of cell biology |
| spellingShingle | Mark Germanos Belinda Yau Matthew Taper Cara Yeoman Amy Wilson Yousun An Jerome Cattin-Ortolá Drew Masler Jason Tong Sheyda Naghiloo Elise J Needham A Gabrielle van der Kraan Kitty Sun Thomas Loudovaris Alexis Diaz-Vegas Mark Larance Helen Thomas Helen von Blume Peter Thorn Michael Ailion Cedric Asensio Melkam Alamerew Kebede Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes iScience Biological sciences Cell biology Organizational aspects of cell biology Specialized functions of cells Functional aspects of cell biology |
| title | Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| title_full | Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| title_fullStr | Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| title_full_unstemmed | Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| title_short | Cab45G trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| title_sort | cab45g trafficking through the insulin secretory pathway is altered in human type 2 diabetes |
| topic | Biological sciences Cell biology Organizational aspects of cell biology Specialized functions of cells Functional aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224029468 |
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