Perilipin is present in islets of Langerhans and protects against lipotoxicity when overexpressed in the beta-cell line INS-1.
Lipids have been shown to play a dual role in pancreatic beta-cells: a lipid-derived signal appears to be necessary for glucose-stimulated insulin secretion, whereas lipid accumulation causes impaired insulin secretion and apoptosis. The ability of the protein perilipin to regulate lipolysis prompted an investigation of the presence of perilipin in the islets of Langerhans. In this study evidence is presented for perilipin expression in rat, mouse, and human islets of Langerhans as well as the rat clonal beta-cell line INS-1. In rat and mouse islets, perilipin was verified to be present in beta-cells. To examine whether the development of lipotoxicity could be prevented by manipulating the conditions for lipid storage in the beta-cell, INS-1 cells with adenoviral-mediated overexpression of perilipin were exposed to lipotoxic conditions for 72 h. In cells exposed to palmitate, perilipin overexpression caused increased accumulation of triacylglycerols and decreased lipolysis compared with control cells. Whereas glucose-stimulated insulin secretion was retained after palmitate exposure in cells overexpressing perilipin, it was completely abolished in control beta-cells. Thus, overexpression of perilipin appears to confer protection against the development of beta-cell dysfunction after prolonged exposure to palmitate by promoting lipid storage and limiting lipolysis.
Borg
Jörgen
J
Department of Experimental Medical Science, Lund University, Lund, Sweden.
Klint
Cecilia
C
Wierup
Nils
N
Ström
Kristoffer
K
Larsson
Sara
S
Sundler
Frank
F
Lupi
Roberto
R
Marchetti
Piero
P
Xu
Guoheng
G
Kimmel
Alan
A
Londos
Constantine
C
Holm
Cecilia
C
D000328:Adult; D000368:Aged; D000818:Animals; D002352:Carrier Proteins; D002460:Cell Line; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D010168:Palmitates / Q000494:pharmacology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D010168:Palmitates; D000070778:Perilipin-1; D010750:Phosphoproteins