Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection
Type 2 diabetes (T2D) is one of the prominent causes of morbidity and mortality in the United States and beyond, reaching global pandemic proportions. One hallmark of T2D is dysfunctional glucose-stimulated insulin secretion from the pancreatic β-cell. Insulin is secreted via the recruitment of insu...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1833 |
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| author | Diti Chatterjee Bhowmick Miwon Ahn Eunjin Oh Rajakrishnan Veluthakal Debbie C. Thurmond |
| author_facet | Diti Chatterjee Bhowmick Miwon Ahn Eunjin Oh Rajakrishnan Veluthakal Debbie C. Thurmond |
| author_sort | Diti Chatterjee Bhowmick |
| collection | DOAJ |
| description | Type 2 diabetes (T2D) is one of the prominent causes of morbidity and mortality in the United States and beyond, reaching global pandemic proportions. One hallmark of T2D is dysfunctional glucose-stimulated insulin secretion from the pancreatic β-cell. Insulin is secreted via the recruitment of insulin secretory granules to the plasma membrane, where the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and SNARE regulators work together to dock the secretory granules and release insulin into the circulation. SNARE proteins and their regulators include the Syntaxins, SNAPs, Sec1/Munc18, VAMPs, and double C2-domain proteins. Recent studies using genomics, proteomics, and biochemical approaches have linked deficiencies of exocytosis proteins with the onset and progression of T2D. Promising results are also emerging wherein restoration or enhancement of certain exocytosis proteins to β-cells improves whole-body glucose homeostasis, enhances β-cell function, and surprisingly, protection of β-cell mass. Intriguingly, overexpression and knockout studies have revealed novel functions of certain exocytosis proteins, like Syntaxin 4, suggesting that exocytosis proteins can impact a variety of pathways, including inflammatory signaling and aging. In this review, we present the conventional and unconventional functions of β-cell exocytosis proteins in normal physiology and T2D and describe how these insights might improve clinical care for T2D. |
| first_indexed | 2024-03-09T00:56:16Z |
| format | Article |
| id | doaj.art-157b373166684f06a97b1c2352da3337 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:56:16Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-157b373166684f06a97b1c2352da33372023-12-11T16:52:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224183310.3390/ijms22041833Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and ProtectionDiti Chatterjee Bhowmick0Miwon Ahn1Eunjin Oh2Rajakrishnan Veluthakal3Debbie C. Thurmond4Department of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Molecular and Cellular Endocrinology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USAType 2 diabetes (T2D) is one of the prominent causes of morbidity and mortality in the United States and beyond, reaching global pandemic proportions. One hallmark of T2D is dysfunctional glucose-stimulated insulin secretion from the pancreatic β-cell. Insulin is secreted via the recruitment of insulin secretory granules to the plasma membrane, where the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and SNARE regulators work together to dock the secretory granules and release insulin into the circulation. SNARE proteins and their regulators include the Syntaxins, SNAPs, Sec1/Munc18, VAMPs, and double C2-domain proteins. Recent studies using genomics, proteomics, and biochemical approaches have linked deficiencies of exocytosis proteins with the onset and progression of T2D. Promising results are also emerging wherein restoration or enhancement of certain exocytosis proteins to β-cells improves whole-body glucose homeostasis, enhances β-cell function, and surprisingly, protection of β-cell mass. Intriguingly, overexpression and knockout studies have revealed novel functions of certain exocytosis proteins, like Syntaxin 4, suggesting that exocytosis proteins can impact a variety of pathways, including inflammatory signaling and aging. In this review, we present the conventional and unconventional functions of β-cell exocytosis proteins in normal physiology and T2D and describe how these insights might improve clinical care for T2D.https://www.mdpi.com/1422-0067/22/4/1833insulin secretionexocytosisSTX4DOC2bβ-cell massβ-cell function |
| spellingShingle | Diti Chatterjee Bhowmick Miwon Ahn Eunjin Oh Rajakrishnan Veluthakal Debbie C. Thurmond Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection International Journal of Molecular Sciences insulin secretion exocytosis STX4 DOC2b β-cell mass β-cell function |
| title | Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection |
| title_full | Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection |
| title_fullStr | Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection |
| title_full_unstemmed | Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection |
| title_short | Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection |
| title_sort | conventional and unconventional mechanisms by which exocytosis proteins oversee β cell function and protection |
| topic | insulin secretion exocytosis STX4 DOC2b β-cell mass β-cell function |
| url | https://www.mdpi.com/1422-0067/22/4/1833 |
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