Loss of beta-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits
| Autor: | Maaike M. Roefs, Heein Song, H. Siebe Spijker, Françoise Carlotti, Erik Bos, Marten A. Engelse, Abraham J. Koster, Ton J. Rabelink, Johanne H. Ellenbroek, Anne Clark, Barbara C. Hansen, Eelco J.P. de Koning |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
MECHANISM medicine.medical_specialty endocrine system Endocrinology Diabetes and Metabolism medicine.medical_treatment Plaque Amyloid Type 2 diabetes MASS Biology Research Support POLYPEPTIDE Glucagon Islets of Langerhans MELLITUS Insulin-Secreting Cells Diabetes mellitus Internal medicine Journal Article Internal Medicine medicine Animals Humans Insulin Non-U.S. Gov't geography geography.geographical_feature_category ALPHA-CELLS Research Support Non-U.S. Gov't DEDIFFERENTIATION CHRONIC HYPERGLYCEMIA medicine.disease Islet Macaca mulatta ENDOCRINE PANCREAS Insulin oscillation Macaca fascicularis DIFFERENTIATION Endocrinology Diabetes Mellitus Type 2 Glucagon-Secreting Cells EUROPEAN SUBJECTS PDX1 Ex vivo |
| Zdroj: | Diabetes. American Diabetes Association Inc. Diabetes, 64(8), 2928-2938 ResearcherID Diabetes, 64(8), 2928. American Diabetes Association Inc. |
| ISSN: | 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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