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Lipid Droplet Accumulation in Human Pancreatic Islets is Dependent Upon Both Donor Age and Health
Diabetes ( IF 6.2 ) Pub Date : 2019-12-13 , DOI: 10.2337/db19-0281
Xin Tong 1 , Chunhua Dai 2 , John T Walker 1 , Gopika G Nair 3 , Arion Kennedy 4 , Rotonya M Carr 5 , Matthias Hebrok 3 , Alvin C Powers 1, 2, 6 , Roland Stein 7
Affiliation  

Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and mouse pancreas over a range of ages and states of diabetes. Very few LDs were found in normal human juvenile pancreatic acinar and islet cells, with numbers subsequently increasing throughout adulthood. While accumulation appeared evenly distributed in postjuvenile acinar and islet cells in donors without diabetes, LDs were enriched in islet α- and β-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell–derived β-cell clusters. In contrast, LD accumulation was nearly undetectable in the adult rodent pancreas, even in hyperglycemic and hyperlipidemic models or 1.5-year-old mice. Taken together, there appear to be significant differences in pancreas islet cell lipid handling between species, and the human juvenile and adult cell populations. Moreover, our results suggest that LD enrichment could be impactful to T2D islet cell function.

中文翻译:

人胰岛中脂滴的积累取决于供体年龄和健康状况

移植到免疫缺陷 NSG 小鼠体内的人类而非小鼠胰岛有效地积累了脂滴 (LD)。因为慢性脂质暴露与胰岛 β 细胞功能障碍有关,我们研究了不同年龄和糖尿病状态下完整人和小鼠胰腺中的 LD 积累。在正常人幼年胰腺腺泡和胰岛细胞中发现的 LD 很少,随后在整个成年期数量不断增加。虽然在未患糖尿病的供体的幼年期后腺泡和胰岛细胞中,积累似乎均匀分布,但 LD 在来自 2 型糖尿病 (T2D) 供体的胰岛 α 和 β 细胞中富集。在由人胚胎细胞衍生的 β 细胞簇产生的胰岛 β 样细胞中也发现了 LD。相比之下,在成年啮齿动物胰腺中几乎检测不到 LD 积累,即使在高血糖和高血脂模型或 1.5 岁的小鼠中。综上所述,物种之间以及人类幼年和成年细胞群之间的胰岛细胞脂质处理似乎存在显着差异。此外,我们的结果表明 LD 富集可能对 T2D 胰岛细胞功能有影响。
更新日期:2019-12-13
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