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MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk
Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent con...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310214/ https://www.ncbi.nlm.nih.gov/pubmed/26895793 http://dx.doi.org/10.2337/db15-1323 |
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author | Kusminski, Christine M. Chen, Shiuhwei Ye, Risheng Sun, Kai Wang, Qiong A. Spurgin, Stephen B. Sanders, Phillip E. Brozinick, Joseph T. Geldenhuys, Werner J. Li, Wen-hong Unger, Roger H. Scherer, Philipp E. |
author_facet | Kusminski, Christine M. Chen, Shiuhwei Ye, Risheng Sun, Kai Wang, Qiong A. Spurgin, Stephen B. Sanders, Phillip E. Brozinick, Joseph T. Geldenhuys, Werner J. Li, Wen-hong Unger, Roger H. Scherer, Philipp E. |
author_sort | Kusminski, Christine M. |
collection | PubMed |
description | Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, β-cell–specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in α-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged α-cells exert potent antiapoptotic effects on β-cells and prevent cellular dysfunction associated with mitoNEET overexpression in β-cells. These observations identify that reduced mitochondrial function in α-cells exerts potently protective effects on β-cells, preserving β-cell viability and mass. |
format | Online Article Text |
id | pubmed-5310214 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-53102142017-06-01 MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk Kusminski, Christine M. Chen, Shiuhwei Ye, Risheng Sun, Kai Wang, Qiong A. Spurgin, Stephen B. Sanders, Phillip E. Brozinick, Joseph T. Geldenhuys, Werner J. Li, Wen-hong Unger, Roger H. Scherer, Philipp E. Diabetes Metabolism Mitochondrial metabolism plays an integral role in glucose-stimulated insulin secretion (GSIS) in β-cells. In addition, the diabetogenic role of glucagon released from α-cells plays a major role in the etiology of both type 1 and type 2 diabetes because unopposed hyperglucagonemia is a pertinent contributor to diabetic hyperglycemia. Titrating expression levels of the mitochondrial protein mitoNEET is a powerful approach to fine-tune mitochondrial capacity of cells. Mechanistically, β-cell–specific mitoNEET induction causes hyperglycemia and glucose intolerance due to activation of a Parkin-dependent mitophagic pathway, leading to the formation of vacuoles and uniquely structured mitophagosomes. Induction of mitoNEET in α-cells leads to fasting-induced hypoglycemia and hypersecretion of insulin during GSIS. MitoNEET-challenged α-cells exert potent antiapoptotic effects on β-cells and prevent cellular dysfunction associated with mitoNEET overexpression in β-cells. These observations identify that reduced mitochondrial function in α-cells exerts potently protective effects on β-cells, preserving β-cell viability and mass. American Diabetes Association 2016-06 2016-03-08 /pmc/articles/PMC5310214/ /pubmed/26895793 http://dx.doi.org/10.2337/db15-1323 Text en © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Metabolism Kusminski, Christine M. Chen, Shiuhwei Ye, Risheng Sun, Kai Wang, Qiong A. Spurgin, Stephen B. Sanders, Phillip E. Brozinick, Joseph T. Geldenhuys, Werner J. Li, Wen-hong Unger, Roger H. Scherer, Philipp E. MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title | MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title_full | MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title_fullStr | MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title_full_unstemmed | MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title_short | MitoNEET-Parkin Effects in Pancreatic α- and β-Cells, Cellular Survival, and Intrainsular Cross Talk |
title_sort | mitoneet-parkin effects in pancreatic α- and β-cells, cellular survival, and intrainsular cross talk |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310214/ https://www.ncbi.nlm.nih.gov/pubmed/26895793 http://dx.doi.org/10.2337/db15-1323 |
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