期刊
DIABETES
卷 69, 期 3, 页码 342-354出版社
AMER DIABETES ASSOC
DOI: 10.2337/db19-0281
关键词
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资金
- JDRF Fellowship [DF-2019-738-A-N]
- National Institutes of Health (NIH)
- Vanderbilt University Medical Center Cell Imaging Shared Resource (National Cancer Institute) [CA-68485]
- National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK] [DK-20593, DK-58404, DK-59637]
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD-15052]
- National Eye Institute [EY08126]
- NIH [F30-DK-118830, AA026302, K08 AA021424, DK-105821, DK-108666, DK-106755, DK-050203, DK-090570]
- NIDDK-supported Human Islet Research Network [RRID: SCR_014393, DK-104211, DK-108120, DK-112232]
- Vanderbilt Diabetes Research and Training Center [DK-20593]
- Kraft Family Fellowship
- JDRF postdoctoral fellowship [1-PNF-2016320-S-B]
- JDRF, Leona M. and Harry B. Helmsley Charitable Trust
- U.S. Department of Veterans Affairs [DK-20593, BX 000666]
- Vanderbilt University Neurochemistry Core [U54 HD083211]
- NIDDK-funded Integrated Islet Distribution Program at the City of Hope (NIH) [DK-098085]
- ADA Foundation [1-17-IBS-140]
Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet beta-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 alpha- and beta-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet beta-like cells produced from human embryonic cell-derived beta-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.
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