Lipid Droplet Accumulation in Human Pancreatic Islets is Dependent Upon Both Donor Age and Health

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 post-juvenile acinar and islet cells in non-diabetic donors, LDs were enriched in islet α and β cells from type 2 diabetes mellitus (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell derived β cell clusters (i.e. termed eBCs). 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 appears 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.