DC Field | Value | Language |
---|---|---|
dc.contributor.author | Spijker, H. Siebe | ko |
dc.contributor.author | Song, Heein | ko |
dc.contributor.author | Ellenbroek, Johanne H. | ko |
dc.contributor.author | Roefs, Maaike M. | ko |
dc.contributor.author | Engelse, Marten A. | ko |
dc.contributor.author | Bos, Erik | ko |
dc.contributor.author | Koster, Abraham J. | ko |
dc.contributor.author | Rabelink, Ton J. | ko |
dc.contributor.author | Hansen, Barbara C. | ko |
dc.contributor.author | Clark, Anne | ko |
dc.contributor.author | Carlotti, Francoise | ko |
dc.contributor.author | de Koning, Eelco J. P. | ko |
dc.date.accessioned | 2015-11-20T07:22:21Z | - |
dc.date.available | 2015-11-20T07:22:21Z | - |
dc.date.created | 2015-08-18 | - |
dc.date.created | 2015-08-18 | - |
dc.date.issued | 2015-08 | - |
dc.identifier.citation | DIABETES, v.64, no.8, pp.2928 - 2938 | - |
dc.identifier.issn | 0012-1797 | - |
dc.identifier.uri | http://hdl.handle.net/10203/200633 | - |
dc.description.abstract | Loss of pancreatic islet beta-cell mass and beta-cell dysfunction are central in the development of type 2 diabetes (T2DM). We recently showed that mature human insulin-containing beta-cells can convert into glucagon-containing alpha-cells ex vivo. This loss of beta-cell identity was characterized by the presence of beta-cell transcription factors (Nkx6.1, Pdx1) in glucagon(+) cells. Here, we investigated whether the loss of beta-cell identity also occurs in vivo, and whether it is related to the presence of (pre)diabetes in humans and nonhuman primates. We observed an eight times increased frequency of insulin(+) cells coexpressing glucagon in donors with diabetes. Up to 5% of the cells that were Nkx6.1(+) but insulin(-) coexpressed glucagon, which represents a five times increased frequency compared with the control group. This increase in bihormonal and Nkx6.1(+)glucagon(+)insulin(-) cells was also found in islets of diabetic macaques. The higher proportion of bihormonal cells and Nkx6.1(+)glucagon(+)insulin(-) cells in macaques and humans with diabetes was correlated with the presence and extent of islet amyloidosis. These data indicate that the loss of beta-cell identity occurs in T2DM and could contribute to the decrease of functional beta-cell mass. Maintenance of beta-cell identity is a potential novel strategy to preserve beta-cell function in diabetes. | - |
dc.language | English | - |
dc.publisher | AMER DIABETES ASSOC | - |
dc.subject | ALPHA-CELLS | - |
dc.subject | CHRONIC HYPERGLYCEMIA | - |
dc.subject | ENDOCRINE PANCREAS | - |
dc.subject | EUROPEAN SUBJECTS | - |
dc.subject | MASS | - |
dc.subject | MELLITUS | - |
dc.subject | DEDIFFERENTIATION | - |
dc.subject | DIFFERENTIATION | - |
dc.subject | POLYPEPTIDE | - |
dc.subject | MECHANISM | - |
dc.title | Loss of beta-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits | - |
dc.type | Article | - |
dc.identifier.wosid | 000358671300030 | - |
dc.identifier.scopusid | 2-s2.0-84942877373 | - |
dc.type.rims | ART | - |
dc.citation.volume | 64 | - |
dc.citation.issue | 8 | - |
dc.citation.beginningpage | 2928 | - |
dc.citation.endingpage | 2938 | - |
dc.citation.publicationname | DIABETES | - |
dc.identifier.doi | 10.2337/db14-1752 | - |
dc.contributor.localauthor | Song, Heein | - |
dc.contributor.nonIdAuthor | Spijker, H. Siebe | - |
dc.contributor.nonIdAuthor | Ellenbroek, Johanne H. | - |
dc.contributor.nonIdAuthor | Roefs, Maaike M. | - |
dc.contributor.nonIdAuthor | Engelse, Marten A. | - |
dc.contributor.nonIdAuthor | Bos, Erik | - |
dc.contributor.nonIdAuthor | Koster, Abraham J. | - |
dc.contributor.nonIdAuthor | Rabelink, Ton J. | - |
dc.contributor.nonIdAuthor | Hansen, Barbara C. | - |
dc.contributor.nonIdAuthor | Clark, Anne | - |
dc.contributor.nonIdAuthor | Carlotti, Francoise | - |
dc.contributor.nonIdAuthor | de Koning, Eelco J. P. | - |
dc.type.journalArticle | Article | - |
dc.subject.keywordPlus | ALPHA-CELLS | - |
dc.subject.keywordPlus | CHRONIC HYPERGLYCEMIA | - |
dc.subject.keywordPlus | ENDOCRINE PANCREAS | - |
dc.subject.keywordPlus | EUROPEAN SUBJECTS | - |
dc.subject.keywordPlus | MASS | - |
dc.subject.keywordPlus | MELLITUS | - |
dc.subject.keywordPlus | DEDIFFERENTIATION | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | POLYPEPTIDE | - |
dc.subject.keywordPlus | MECHANISM | - |
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