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| Item Type: | Article |
|---|---|
| Title: | Haploinsufficiency of Insm1 impairs postnatal baseline β-cell mass |
| Creators Name: | Tao, W., Zhang, Y., Ma, L., Deng, C., Duan, H., Liang, X., Liao, R., Lin, S., Nie, T., Chen, W., Wang, C., Birchmeier, C. and Jia, S. |
| Abstract: | Baseline beta-cell mass is established during the early postnatal period when beta cells expand. Here, we show that heterozygous ablation of decreases baseline beta-cell mass and subsequently impairs glucose tolerance. When exposed to a high-fat diet or on an background, glucose intolerance was more severe in mice compared to mice, although no further decrease in the beta-cell mass was detected. In islets of early postnatal mice, cell cycle was prolonged in beta cells due to downregulation of the cell cycle gene Although Insm1 had a low affinity for the promoter compared to other binding sites, binding affinity was strongly dependent on Insm1 levels. We observed dramatically decreased binding of Insm1 to the promoter after downregulation of expression. Furthermore, downregulation of resulted in a prolonged cell cycle and overexpression of Ccnd1 rescued cell cycle abnormalities observed in Insm1-deficient beta cells. We conclude that decreases in Insm1 interfere with beta-cell specification during the early postnatal period and impair glucose homeostasis during metabolic stress in adults. Insm1 levels are therefore a factor that can influence the development of diabetes. |
| Keywords: | Blood Glucose, Cell Cycle, Cyclin D1, DNA-Binding Proteins, High-Fat, Diet, Haploinsufficiency, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Promoter Regions, Genetic, Transcription Factors, Transgenic, Mice, Mice, Animals |
| Source: | Diabetes |
| ISSN: | 0012-1797 |
| Publisher: | American Diabetes Association |
| Volume: | 67 |
| Number: | 12 |
| Page Range: | 2615-2625 |
| Date: | December 2018 |
| Additional Information: | Copyright © 2018 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. More information is available at http://www.diabetesjournals.org/content/license. |
| Official Publication: | https://doi.org/10.2337/db17-1330 |
| PubMed: | View item in PubMed |
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