Glucolipotoxicity in INS-1E cells is counteracted by carnitine palmitoyltransferase 1 over-expression.
Effects of non-esterified fatty acids (FAs) are accentuated when applied together with elevated glucose through preferential use of glucose as fuel, which leads to decreased oxidation of FAs. We examined how over-expression of the mitochondrial FA transporter carnitine palmitoyltransferase 1 (CPT1) affects glucose-stimulated insulin secretion (GSIS), apoptosis and ER stress in INS-1E cells cultured in the presence of elevated levels of glucose and palmitate. INS-1E cells were infected with Tet-ON regulated adenovirus containing CPT1 and cultured for 48h in the presence of 0.5mM palmitate and 20mM glucose. Over-expressing CPT1 lowered basal insulin secretion in a dose-dependent manner thereby improving GSIS from INS-1E cells. Also, apoptosis was alleviated and ER-stress markers p-eIF2alpha and CHOP were decreased in cells over-expressing CPT1. We conclude that regulated over-expression of CPT1 is beneficial for glucolipotoxic beta-cells.
Sol
E Maria
EM
Department of Medical Cell Biology, Uppsala University, Box 571, Husargatan 3, 75123 Uppsala, Sweden. E-ri.Sol@mcb.uu.se
Sargsyan
Ernest
E
Akusjärvi
Göran
G
Bergsten
Peter
P
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000633:toxicity; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D010168:Palmitates / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D051742:Transcription Factor CHOP / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates; D051742:Transcription Factor CHOP; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose