دورية أكاديمية
Loss of β-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits.
| العنوان: | Loss of β-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits. |
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| المؤلفون: | Spijker HS; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., Song H; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea., Ellenbroek JH; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., Roefs MM; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., Engelse MA; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., Bos E; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands., Koster AJ; Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands., Rabelink TJ; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., Hansen BC; Departments of Internal Medicine and Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, FL., Clark A; Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, U.K., Carlotti F; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands., de Koning EJ; Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands Hubrecht Institute, Utrecht, the Netherlands e.dekoning@lumc.nl. |
| المصدر: | Diabetes [Diabetes] 2015 Aug; Vol. 64 (8), pp. 2928-38. Date of Electronic Publication: 2015 Apr 27. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Alexandria, VA : American Diabetes Association Original Publication: [New York, American Diabetes Association] |
| مواضيع طبية MeSH: | Diabetes Mellitus, Type 2/*pathology , Glucagon-Secreting Cells/*pathology , Insulin-Secreting Cells/*pathology , Islets of Langerhans/*pathology , Plaque, Amyloid/*pathology, Animals ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/physiopathology ; Glucagon/metabolism ; Glucagon-Secreting Cells/metabolism ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/metabolism ; Islets of Langerhans/physiopathology ; Macaca fascicularis ; Macaca mulatta ; Male ; Plaque, Amyloid/metabolism ; Plaque, Amyloid/physiopathology |
| مستخلص: | Loss of pancreatic islet β-cell mass and β-cell dysfunction are central in the development of type 2 diabetes (T2DM). We recently showed that mature human insulin-containing β-cells can convert into glucagon-containing α-cells ex vivo. This loss of β-cell identity was characterized by the presence of β-cell transcription factors (Nkx6.1, Pdx1) in glucagon(+) cells. Here, we investigated whether the loss of β-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 β-cell identity occurs in T2DM and could contribute to the decrease of functional β-cell mass. Maintenance of β-cell identity is a potential novel strategy to preserve β-cell function in diabetes. (© 2015 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.) |
| التعليقات: | Comment in: Diabetes. 2015 Aug;64(8):2698-700. (PMID: 26207032) |
| المشرفين على المادة: | 0 (Insulin) 9007-92-5 (Glucagon) |
| تواريخ الأحداث: | Date Created: 20150429 Date Completed: 20151009 Latest Revision: 20220321 |
| رمز التحديث: | 20230127 |
| DOI: | 10.2337/db14-1752 |
| PMID: | 25918235 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1939-327X |
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| DOI: | 10.2337/db14-1752 |