LAUSR

The formation of cross-linked protein aggregates such as lipofuscin is a typical hallmark of cellular aging and especially affects long-living and postmitotic cells such as neurons and skeletal muscle cells. Lipofuscin can neither be degraded nor exocytosed, it is a prominent source of oxidants and able to inhibit proteolytic systems such as the 20 S proteasome and the autophagy-lysosomal pathway. Adult pancreatic β-cells are also considered to be long-living cells which may last for years or even a life-time. It was shown, that these cells are also characterized by an age-dependent increase in lipofuscin content, but little is known about the process of accumulating protein aggregates and their impact on β-cell functionality. We used the pancreatic β-cell line MIN6 with a well-established artificial lipofuscin to investigate different parameters of β-cell functionality and the impact of lipofuscin on the insulin-degrading enzyme (IDE). Interestingly, we observed both, a significantly higher insulin amount and secretion in the aggregate-fed MIN6 cells. While the expression of insulin does not seem to be affected by lipofuscin treatment, the presence of lipofuscin is able to decrease the activity of IDE by an unknown mechanism.