β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?
<div><p>Diabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type...
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2022
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| _version_ | 1864513519231172608 |
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| author | Abdoulaye Diane (14152749) |
| author2 | Noora Ali Al-Shukri (18372429) Razik Bin Abdul Mu-u-min (18372432) Heba H. Al-Siddiqi (17733783) |
| author2_role | author author author |
| author_facet | Abdoulaye Diane (14152749) Noora Ali Al-Shukri (18372429) Razik Bin Abdul Mu-u-min (18372432) Heba H. Al-Siddiqi (17733783) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abdoulaye Diane (14152749) Noora Ali Al-Shukri (18372429) Razik Bin Abdul Mu-u-min (18372432) Heba H. Al-Siddiqi (17733783) |
| dc.date.none.fl_str_mv | 2022-04-09T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1186/s12967-022-03327-5 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/_-cell_mitochondria_in_diabetes_mellitus_a_missing_puzzle_piece_in_the_generation_of_hPSC-derived_pancreatic_-cells_/25609440 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics β-cell Pancreas Mitochondria Diabetes mellitus hPSC-derived β-cells Differentiation Glucose-stimulated insulin secretion (GSIS) |
| dc.title.none.fl_str_mv | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>Diabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type 2 diabetes (T2DM). Because impaired insulin secretion due to dysfunction or loss of pancreatic β-cells underlies different types of diabetes, research has focused its effort towards the generation of pancreatic β-cells from human pluripotent stem cell (hPSC) as a potential source of cells to compensate for insulin deficiency. However, many protocols developed to differentiate hPSCs into insulin-expressing β-cells in vitro have generated hPSC-derived β-cells with either immature phenotype such as impaired glucose-stimulated insulin secretion (GSIS) or a weaker response to GSIS than cadaveric islets. In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring refined control of GSIS. Defects in β-cell mitochondrial metabolism and function impair this metabolic coupling. In the present review, we highlight the role of mitochondria in metabolism secretion coupling in the β-cells and summarize the evidence accumulated for the implication of mitochondria in β-cell dysfunction in DM and consequently, how targeting mitochondria function might be a new and interesting strategy to further perfect the differentiation protocol for generation of mature and functional hPSC-derived β-cells with GSIS profile similar to human cadaveric islets for drug screening or potentially for cell therapy.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Journal of Translational Medicine<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12967-022-03327-5" target="_blank">https://dx.doi.org/10.1186/s12967-022-03327-5</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_cb6e727a75c422a0ef3832290d7bc2c6 |
| identifier_str_mv | 10.1186/s12967-022-03327-5 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25609440 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells?Abdoulaye Diane (14152749)Noora Ali Al-Shukri (18372429)Razik Bin Abdul Mu-u-min (18372432)Heba H. Al-Siddiqi (17733783)Biological sciencesBiochemistry and cell biologyGeneticsβ-cellPancreasMitochondriaDiabetes mellitushPSC-derived β-cellsDifferentiationGlucose-stimulated insulin secretion (GSIS)<div><p>Diabetes mellitus (DM), currently affecting 463 million people worldwide is a chronic disease characterized by impaired glucose metabolism resulting from the loss or dysfunction of pancreatic β-cells with the former preponderating in type 1 diabetes (T1DM) and the latter in type 2 diabetes (T2DM). Because impaired insulin secretion due to dysfunction or loss of pancreatic β-cells underlies different types of diabetes, research has focused its effort towards the generation of pancreatic β-cells from human pluripotent stem cell (hPSC) as a potential source of cells to compensate for insulin deficiency. However, many protocols developed to differentiate hPSCs into insulin-expressing β-cells in vitro have generated hPSC-derived β-cells with either immature phenotype such as impaired glucose-stimulated insulin secretion (GSIS) or a weaker response to GSIS than cadaveric islets. In pancreatic β-cells, mitochondria play a central role in coupling glucose metabolism to insulin exocytosis, thereby ensuring refined control of GSIS. Defects in β-cell mitochondrial metabolism and function impair this metabolic coupling. In the present review, we highlight the role of mitochondria in metabolism secretion coupling in the β-cells and summarize the evidence accumulated for the implication of mitochondria in β-cell dysfunction in DM and consequently, how targeting mitochondria function might be a new and interesting strategy to further perfect the differentiation protocol for generation of mature and functional hPSC-derived β-cells with GSIS profile similar to human cadaveric islets for drug screening or potentially for cell therapy.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Journal of Translational Medicine<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1186/s12967-022-03327-5" target="_blank">https://dx.doi.org/10.1186/s12967-022-03327-5</a></p>2022-04-09T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12967-022-03327-5https://figshare.com/articles/journal_contribution/_-cell_mitochondria_in_diabetes_mellitus_a_missing_puzzle_piece_in_the_generation_of_hPSC-derived_pancreatic_-cells_/25609440CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256094402022-04-09T03:00:00Z |
| spellingShingle | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? Abdoulaye Diane (14152749) Biological sciences Biochemistry and cell biology Genetics β-cell Pancreas Mitochondria Diabetes mellitus hPSC-derived β-cells Differentiation Glucose-stimulated insulin secretion (GSIS) |
| status_str | publishedVersion |
| title | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| title_full | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| title_fullStr | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| title_full_unstemmed | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| title_short | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| title_sort | β-cell mitochondria in diabetes mellitus: a missing puzzle piece in the generation of hPSC-derived pancreatic β-cells? |
| topic | Biological sciences Biochemistry and cell biology Genetics β-cell Pancreas Mitochondria Diabetes mellitus hPSC-derived β-cells Differentiation Glucose-stimulated insulin secretion (GSIS) |