EFFECT OF FATTY-ACIDS ON INSULIN RELEASE - ROLE OF CHAIN-LENGTH AND DEGREE OF UNSATURATION

The purpose of the present study was to examine the role played by str uctural differences among fatty acids in their effect on insulin secre tion by isolated perifused murine islets. Insulin secretion measured b y radioimmunoassay was assessed either as total insulin output (ng.6 i slets(-1) 20 min(-1)) or as percent of basal insulin secretion. Raisin g the glucose concentration from a basal 5.5 to 27.7 mM caused an incr ease of insulin output from 6.69 +/- 1.59 to 19.92 +/- 4.99 ng 6.islet s(-1).20 min(-1) (P < 0.05) in control (untreated) islets. However, af ter 20-min exposure of islets to 5 mM 16:0 or 18:2, the effect of 27.7 mM glucose was enhanced or diminished, respectively. Basal insulin ou tput (100% basal) changed to 44 +/- 10% basal (P < 0.005) with the add ition of 5 mM 4:0 but was not altered when 4:0 was replaced by 6:0. In sulin output increased modestly with 5 mM 8:0 but significantly (P < 0 .05) with 10:0 until a maximal of 280 +/- 24% basal with 12:0 (P < 0.0 1), then fell to 110 +/- 18 and 93 +/- 15% basal(P < 0.05) with 14:0 a nd 16:0, respectively. The addition of 5 mM 18:0 inhibited insulin sec retion to 30 +/- 10% of basal (P < 0.003), and this effect was not cau sed by fatty acid interference with insulin assay. In the presence of 2 mM of each fatty acid, insulin secretion was unaffected by 18:0 but increased to 137 +/- 29, 156 +/- 12 (P < 0.05), and 206 +/- 16% (P < 0 .01) basal, with 18:1, 18:2, and 18:3, respectively. The 18:3 and 20:4 (2 mM each) were equipotent. In conclusion, the effect of fatty acids on insulin release is dependent both on their chain length and degree of unsaturation.