Role of lysosomes in insulin signaling and glucose uptake in cultured rat podocytes

Biochem Biophys Res Commun. 2023 Sep 6;679:145-159. doi: 10.1016/j.bbrc.2023.09.012. Online ahead of print.ABSTRACTPodocytes are sensitive to insulin, which governs the functional and structural integrity of podocytes that are essential for proper function of the glomerular filtration barrier. Lysosomes are acidic organelles that are implicated in regulation of the insulin signaling pathway. Cathepsin D (CTPD) and lysosome-associated membrane protein 1 (LAMP1) are major lysosomal proteins that reflect the functional state of lysosomes. However, the effect of insulin on lysosome activity and role of lysosomes in the regulation of insulin-dependent glucose uptake in podocytes are unknown. Our studies showed that the short-term incubation of podocytes with insulin decreased LAMP1 and CTPD mRNA levels. Insulin and bafilomycin A1 reduced both the amounts of LAMP1 and CTPD proteins and activity of CTPD, which were associated with a decrease in the fluorescence intensity of lysosomes that were labeled with LysoTracker. Bafilomycin A1 inhibited insulin-dependent endocytosis of the insulin receptor and increased the amounts of the insulin receptor and glucose transporter 4 on the cell surface of podocytes. Bafilomycin A1 also inhibited insulin-dependent glucose uptake despite an increase in the amount of glucose transporter 4 in the plasma membrane of podocytes. These results suggest that lysosomes are signaling hubs that may be involved in the coupling of insulin signaling with the r...

Source: Biochemical and Biophysical Research communications - September 11, 2023 Category: Biochemistry Authors: Patrycja Rachubik Dorota Rogacka Irena Audzeyenka Marlena Typiak Magdalena Wysocka Maria Szrejder Adam Lesner Agnieszka Piwkowska Source Type: research