Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes
<p>To discuss the current understanding of “β cell identity” and factors underlying altered identity of pancreatic β cells in diabetes, especially in humans. Altered identity of β cells due to dedifferentiation and/or transdifferentiation has been proposed as a mechanism of loss of β cells in...
محفوظ في:
| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | |
| منشور في: |
2019
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| الموضوعات: | |
| الوسوم: |
إضافة وسم
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| _version_ | 1864513567205621760 |
|---|---|
| author | Abu Saleh Md Moin (6189512) |
| author2 | Alexandra E. Butler (6189536) |
| author2_role | author |
| author_facet | Abu Saleh Md Moin (6189512) Alexandra E. Butler (6189536) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abu Saleh Md Moin (6189512) Alexandra E. Butler (6189536) |
| dc.date.none.fl_str_mv | 2019-08-10T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s11892-019-1194-6 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Alterations_in_Beta_Cell_Identity_in_Type_1_and_Type_2_Diabetes/21597642 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical biotechnology β Cell Dedifferentiation Transdifferentiation Type 1 diabetes Type 2 diabetes Pancreas |
| dc.title.none.fl_str_mv | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p>To discuss the current understanding of “β cell identity” and factors underlying altered identity of pancreatic β cells in diabetes, especially in humans. Altered identity of β cells due to dedifferentiation and/or transdifferentiation has been proposed as a mechanism of loss of β cells in diabetes. In dedifferentiation, β cells do not undergo apoptosis; rather, they lose their identity and function. Dedifferentiation is well characterized by the decrease in expression of key β cell markers such as genes encoding major transcription factors, e.g., MafA, NeuroD1, Nkx6.1, and Foxo1, and an increase in atypical or “disallowed” genes for β cells such as lactate dehydrogenase, monocarboxylate transporter MCT1, or progenitor cell genes (Neurog3, Pax4, or Sox9). Moreover, altered identity of mature β cells in diabetes also involves transdifferentiation of β cells into other islet hormone producing cells. For example, overexpression of α cell specific transcription factor Arx or ablation of Pdx1 resulted in an increase of α cell numbers and a decrease in β cell numbers in rodents. The frequency of α-β double-positive cells was also prominent in human subjects with T2D. These altered identities of β cells likely serve as a compensatory response to enhance function/expand cell numbers and may also camouflage/protect cells from ongoing stress. However, it is equally likely that this may be a reflection of new cell formation as a frank regenerative response to ongoing tissue injury. Physiologically, all these responses are complementary. In diabetes, (1) endocrine identity recapitulates the less mature/less-differentiated fetal/neonatal cell type, possibly representing an adaptive mechanism; (2) residual β cells may be altered in their subtype proportions or other molecular features; (3) in humans, “altered identity” is a preferable term to dedifferentiation as their cellular fate (differentiated cells losing identity or progenitors becoming more differentiated) is unclear as yet.</p><h2>Other Information</h2> <p> Published in: Current Diabetes Reports<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="http://dx.doi.org/10.1007/s11892-019-1194-6" target="_blank">http://dx.doi.org/10.1007/s11892-019-1194-6</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_273b20f0ebcbccc9b52822e361724565 |
| identifier_str_mv | 10.1007/s11892-019-1194-6 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/21597642 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Alterations in Beta Cell Identity in Type 1 and Type 2 DiabetesAbu Saleh Md Moin (6189512)Alexandra E. Butler (6189536)Biomedical and clinical sciencesClinical sciencesMedical biochemistry and metabolomicsMedical biotechnologyβ CellDedifferentiationTransdifferentiationType 1 diabetesType 2 diabetesPancreas<p>To discuss the current understanding of “β cell identity” and factors underlying altered identity of pancreatic β cells in diabetes, especially in humans. Altered identity of β cells due to dedifferentiation and/or transdifferentiation has been proposed as a mechanism of loss of β cells in diabetes. In dedifferentiation, β cells do not undergo apoptosis; rather, they lose their identity and function. Dedifferentiation is well characterized by the decrease in expression of key β cell markers such as genes encoding major transcription factors, e.g., MafA, NeuroD1, Nkx6.1, and Foxo1, and an increase in atypical or “disallowed” genes for β cells such as lactate dehydrogenase, monocarboxylate transporter MCT1, or progenitor cell genes (Neurog3, Pax4, or Sox9). Moreover, altered identity of mature β cells in diabetes also involves transdifferentiation of β cells into other islet hormone producing cells. For example, overexpression of α cell specific transcription factor Arx or ablation of Pdx1 resulted in an increase of α cell numbers and a decrease in β cell numbers in rodents. The frequency of α-β double-positive cells was also prominent in human subjects with T2D. These altered identities of β cells likely serve as a compensatory response to enhance function/expand cell numbers and may also camouflage/protect cells from ongoing stress. However, it is equally likely that this may be a reflection of new cell formation as a frank regenerative response to ongoing tissue injury. Physiologically, all these responses are complementary. In diabetes, (1) endocrine identity recapitulates the less mature/less-differentiated fetal/neonatal cell type, possibly representing an adaptive mechanism; (2) residual β cells may be altered in their subtype proportions or other molecular features; (3) in humans, “altered identity” is a preferable term to dedifferentiation as their cellular fate (differentiated cells losing identity or progenitors becoming more differentiated) is unclear as yet.</p><h2>Other Information</h2> <p> Published in: Current Diabetes Reports<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="http://dx.doi.org/10.1007/s11892-019-1194-6" target="_blank">http://dx.doi.org/10.1007/s11892-019-1194-6</a></p>2019-08-10T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s11892-019-1194-6https://figshare.com/articles/journal_contribution/Alterations_in_Beta_Cell_Identity_in_Type_1_and_Type_2_Diabetes/21597642CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215976422019-08-10T06:00:00Z |
| spellingShingle | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes Abu Saleh Md Moin (6189512) Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical biotechnology β Cell Dedifferentiation Transdifferentiation Type 1 diabetes Type 2 diabetes Pancreas |
| status_str | publishedVersion |
| title | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| title_full | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| title_fullStr | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| title_full_unstemmed | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| title_short | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| title_sort | Alterations in Beta Cell Identity in Type 1 and Type 2 Diabetes |
| topic | Biomedical and clinical sciences Clinical sciences Medical biochemistry and metabolomics Medical biotechnology β Cell Dedifferentiation Transdifferentiation Type 1 diabetes Type 2 diabetes Pancreas |