Mono-unsaturated fatty acids protect against beta-cell apoptosis induced by saturated fatty acids, serum withdrawal or cytokine exposure.
Long-chain saturated fatty acids are cytotoxic to pancreatic beta-cells while shorter-chain saturated and long-chain unsaturated molecules are better tolerated. Mono-unsaturated fatty acids are not, however, inert since they inhibit the pro-apoptotic effects of saturated molecules. In the present work we show that the mono-unsaturates palmitoleate (C16:1) or oleate (C18:1) also cause marked inhibition of apoptosis induced by exposure of clonal BRIN-BD11 beta-cells to serum withdrawal or a combination of interleukin-1beta plus interferon-gamma. This response was dose-dependent and not accompanied by changes in NO formation. Taken together, the results suggest that mono-unsaturated fatty acids regulate a distal step common to several apoptotic pathways in pancreatic beta-cells.
Institute of Biomedical and Clinical Science, Peninsula Medical School, Room N32, ITTC Building, Tamar Science Park, Plymouth, PL6 8BX, UK.
Hannah J
HJ
Welters
Moh
M
Tadayyon
John H B
JH
Scarpello
Stephen A
SA
Smith
Noel G
NG
Morgan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002210:Caprylates / Q000633:toxicity; D002417:Cattle; D002999:Clone Cells; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000633:toxicity*; D005229:Fatty Acids, Monounsaturated / Q000037:antagonists & inhibitors*; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019814:Myristic Acid / Q000633:toxicity; D009569:Nitric Oxide / Q000096:biosynthesis; D009829:Oleic Acids / Q000037:antagonists & inhibitors; D010169:Palmitic Acids / Q000037:antagonists & inhibitors; D051381:Rats; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013229:Stearic Acids / Q000633:toxicity; D013329:Structure-Activity Relationship; D013997:Time Factors
D002210:Caprylates; D016895:Culture Media, Serum-Free; D016207:Cytokines; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D007375:Interleukin-1; D009829:Oleic Acids; D010169:Palmitic Acids; D013229:Stearic Acids; D019814:Myristic Acid; C008757:palmitoleic acid; D012710:Serum Albumin, Bovine; D009569:Nitric Oxide; D007371:Interferon-gamma; C031492:octanoic acid