期刊
DIABETES
卷 67, 期 11, 页码 2254-2267出版社
AMER DIABETES ASSOC
DOI: 10.2337/db18-0201
关键词
-
资金
- Swiss National Science Foundation [310030-169480]
- Fondation Francophone pour la Recherche sur le Diabete - Federation Francaise des Diabetiques
- Eli Lilly Co.
- Merck Sharp Dohme
- Novo Nordisk
- Sanofi
- Canadian Institutes of Health Research
- National Health and Medical Research Council of Australia
- INSERM
- Universite Cote d'Azur
- Conseil Regional de Provence-Alpes-Cote d'Azur
- Conseil General des Alpes-Maritimes
- Aviesan/AstraZeneca
- Agence Nationale de la Recherche (ANR) [ANR-RPV12004AAA, ANR-11-LABX-0028-01]
- European Foundation for the Study of Diabetes (EFSD)
- Lilly European Diabetes Research Programme
- AstraZeneca
Pancreatic beta-cell expansion throughout the neonatal period is essential to generate the appropriate mass of insulin-secreting cells required to maintain blood glucose homeostasis later in life. Hence, defects in this process can predispose to diabetes development during adulthood. Global profiling of transcripts in pancreatic islets of newborn and adult rats revealed that the transcription factor E2F1 controls expression of the long noncoding RNA H19, which is profoundly downregulated during the postnatal period. H19 silencing decreased beta-cell expansion in newborns, whereas its re-expression promoted proliferation of beta-cells in adults via a mechanism involving the microRNA let-7 and the activation of Akt. The offspring of rats fed a low-protein diet during gestation and lactation display a small beta-cell mass and an increased risk of developing diabetes during adulthood. We found that the islets of newborn rats born to dams fed a low-protein diet express lower levels of H19 than those born to dams that did not eat a low-protein diet. Moreover, we observed that H19 expression increases in islets of obese mice under conditions of increased insulin demand. Our data suggest that the long noncoding RNA H19 plays an important role in postnatal beta-cell mass expansion in rats and contributes to the mechanisms compensating for insulin resistance in obesity.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据