Chronic effects of different fatty acids and leptin in INS-1 cells.
The effects of long-term exposure of a pancreatic beta cell line, INS-1, to major free fatty acids (FFA; palmitic acid, oleic acid and linoleic acid) and leptin on insulin secretion and cell viability by C,N-diphenyl-N'-4,5 dimethylthiazol 2-yl tetrazolium bromide (MTT) assay were examined. The cells were incubated with 1 mmol/l of each FFA and 25 or 100 ng/ml leptin, alone or in combination, for 4, 24 or 48 h before the insulin secretion experiments. Palmitic acid (C 16:0) significantly suppressed cell viability, and suppressed insulin secretion at 24 h. Treatment with oleic acid (C 18:1) or linoleic acid (C 18:2) enhanced basal insulin secretion and diminished glucose-stimulated insulin secretion (GSIS) at 48 h. In these groups, there were no differences in cell viability as compared to cells treated without FFA. Leptin did not affect insulin secretion at 4, 24 and 48 h, and in the cells co-treated with FFA and leptin, leptin did not ameliorate lipotoxicity. These results suggest that, in INS-1 cells, different FFA have different patterns of lipotoxicity with chronic exposure, and leptin has little direct effect on insulin secretion.
Kawai
T
T
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. asmd@med.keio.ac.jp
Hirose
H
H
Seto
Y
Y
Fujita
H
H
Saruta
T
T
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans; D007700:Kinetics; D020738:Leptin / Q000494:pharmacology*; D019787:Linoleic Acid / Q000494:pharmacology; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D011994:Recombinant Proteins; D019301:Oleic Acid; D019308:Palmitic Acid; D019787:Linoleic Acid