Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells
Background/Aims: The lack of available beta cells greatly limits the use of beta cell transplantation as a therapy for diabetes. Thus, generation of beta cells from other sources is substantially required. Pax4 has been shown to induce reprograming of alpha cells into beta cells during embryogenesis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-07-01
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| Series: | Cellular Physiology and Biochemistry |
| Subjects: | |
| Online Access: | http://www.karger.com/Article/FullText/430146 |
| _version_ | 1818517202682249216 |
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| author | Ling Chen Jing Zhang Zhuo Zhang Yaping Chu Bing Song Wang Cai |
| author_facet | Ling Chen Jing Zhang Zhuo Zhang Yaping Chu Bing Song Wang Cai |
| author_sort | Ling Chen |
| collection | DOAJ |
| description | Background/Aims: The lack of available beta cells greatly limits the use of beta cell transplantation as a therapy for diabetes. Thus, generation of beta cells from other sources is substantially required. Pax4 has been shown to induce reprograming of alpha cells into beta cells during embryogenesis. Nevertheless, whether expression of Pax4 in adult alpha cells could trigger this alpha-to-beta cell reprogramming is unknown. Methods: Here we generated an adeno-associated virus carrying Pax4 and GFP under a CMV promoter (AAV-Pax4). We used AAV-Pax4 to transduce a mouse alpha cell line in vitro, and to transduce primary alpha cells in diabetic mice. Reprogramming was examined by double immunostaining and by changes in beta cell number. The effects on blood glucose were evaluated by fasting blood glucose and glucose response. Results: In vitro, Pax4 overexpression neither induced insulin expression, nor suppressed glucagon expression in alpha cells. In vivo, Pax4 overexpression failed to increase beta cell number, and did not alter hyperglycemia and glucose response in diabetic mice. Conclusion: Pax4 expression is not sufficient to transduce pancreatic alpha cells into beta cells. Overexpression of Pax4 in alpha cells may not increase functional beta cell number in diabetic patients. |
| first_indexed | 2024-12-11T00:53:00Z |
| format | Article |
| id | doaj.art-90f4a3c647bc4ae1ade0cfda0ee47cc4 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-11T00:53:00Z |
| publishDate | 2015-07-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-90f4a3c647bc4ae1ade0cfda0ee47cc42022-12-22T01:26:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013651735174210.1159/000430146430146Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta CellsLing ChenJing ZhangZhuo ZhangYaping ChuBing SongWang CaiBackground/Aims: The lack of available beta cells greatly limits the use of beta cell transplantation as a therapy for diabetes. Thus, generation of beta cells from other sources is substantially required. Pax4 has been shown to induce reprograming of alpha cells into beta cells during embryogenesis. Nevertheless, whether expression of Pax4 in adult alpha cells could trigger this alpha-to-beta cell reprogramming is unknown. Methods: Here we generated an adeno-associated virus carrying Pax4 and GFP under a CMV promoter (AAV-Pax4). We used AAV-Pax4 to transduce a mouse alpha cell line in vitro, and to transduce primary alpha cells in diabetic mice. Reprogramming was examined by double immunostaining and by changes in beta cell number. The effects on blood glucose were evaluated by fasting blood glucose and glucose response. Results: In vitro, Pax4 overexpression neither induced insulin expression, nor suppressed glucagon expression in alpha cells. In vivo, Pax4 overexpression failed to increase beta cell number, and did not alter hyperglycemia and glucose response in diabetic mice. Conclusion: Pax4 expression is not sufficient to transduce pancreatic alpha cells into beta cells. Overexpression of Pax4 in alpha cells may not increase functional beta cell number in diabetic patients.http://www.karger.com/Article/FullText/430146Beta cellsPax4Alpha cellsAlpha-to-beta cell reprogrammingDiabetes |
| spellingShingle | Ling Chen Jing Zhang Zhuo Zhang Yaping Chu Bing Song Wang Cai Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells Cellular Physiology and Biochemistry Beta cells Pax4 Alpha cells Alpha-to-beta cell reprogramming Diabetes |
| title | Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells |
| title_full | Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells |
| title_fullStr | Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells |
| title_full_unstemmed | Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells |
| title_short | Pax4 Expression does not Transduce Pancreatic Alpha Cells to Beta Cells |
| title_sort | pax4 expression does not transduce pancreatic alpha cells to beta cells |
| topic | Beta cells Pax4 Alpha cells Alpha-to-beta cell reprogramming Diabetes |
| url | http://www.karger.com/Article/FullText/430146 |
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