Palmitate-induced beta cell apoptosis and development of the unfolded protein response
(English)Manuscript (Other academic)
Elevated levels of lipids are detrimental for beta cell function and mass. Accentuation or attenuation of these effects has been proposed to depend on promoting lipid accumulation or oxidation, respectively. In the present study we investigated if enhanced and reduced beta cell apoptosis observed in response to altered lipid metabolism involves modulation of the unfolded protein response (UPR). INS-1E cells were cultured in the presence of 0.5 mM palmitate and 3, 11 or 25 mM glucose for 3 or 24 hours. Cells cultured in the presence of palmitate and 11 mM glucose were additionally exposed to AMPK-agonist AICAR or CPT1-inhibitior etomoxir. After culture, apoptosis and expression levels of UPR markers were determined. Apoptosis was induced 3- and 5-fold in cells cultured in the presence of palmitate and 11 or 25 mM glucose, respectively. No induction was observed in cells cultured in the presence of palmitate and 3 mM glucose. Despite the glucose-dependency of palmitate-induced beta cell apoptosis, expression levels of UPR markers were not altered by varying the glucose concentration. In addition, although AICAR reduced apoptosis in palmitate-treated cells and etomoxir accentuated apoptosis in cells exposed to the fatty acid, UPR markers were neither affected by AICAR nor etomoxir. We conclude that under conditions, which direct palmitate-exposed cells either towards lipid oxidation or accumulation, apoptosis but not activation of the UPR is altered. It is hypothesized that palmitate-induced activation of the UPR is not a major determinant of apoptosis in beta cells exposed to the fatty acid.
ER stress, unfolded protein response, glucolipotoxicity, apoptosis, INS-1E pancreatic beta cells
Cell and Molecular Biology
Research subject Medical Cell Biology
IdentifiersURN: urn:nbn:se:uu:diva-98363OAI: oai:DiVA.org:uu-98363DiVA: diva2:174253