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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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Autores principales: Chatterjee Bhowmick, Diti, Ahn, Miwon, Oh, Eunjin, Veluthakal, Rajakrishnan, Thurmond, Debbie C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918544/
https://www.ncbi.nlm.nih.gov/pubmed/33673206
http://dx.doi.org/10.3390/ijms22041833
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author Chatterjee Bhowmick, Diti
Ahn, Miwon
Oh, Eunjin
Veluthakal, Rajakrishnan
Thurmond, Debbie C.
author_facet Chatterjee Bhowmick, Diti
Ahn, Miwon
Oh, Eunjin
Veluthakal, Rajakrishnan
Thurmond, Debbie C.
author_sort Chatterjee Bhowmick, Diti
collection PubMed
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.
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spelling pubmed-79185442021-03-02 Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection Chatterjee Bhowmick, Diti Ahn, Miwon Oh, Eunjin Veluthakal, Rajakrishnan Thurmond, Debbie C. Int J Mol Sci Review 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. MDPI 2021-02-12 /pmc/articles/PMC7918544/ /pubmed/33673206 http://dx.doi.org/10.3390/ijms22041833 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Chatterjee Bhowmick, Diti
Ahn, Miwon
Oh, Eunjin
Veluthakal, Rajakrishnan
Thurmond, Debbie C.
Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918544/
https://www.ncbi.nlm.nih.gov/pubmed/33673206
http://dx.doi.org/10.3390/ijms22041833
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