INVITRO LIPID-METABOLISM IN THE RAT PANCREAS .2. EFFECTS OF SECRETAGOGUES ON FATTY-ACID METABOLISM, NET LIPOLYSIS AND ATP LEVELS

1. 1. The concentration of carbamylcholine, bombesin, pancreozymin, pentagastrin and secretin evoking a similar 4-5-fold maximal increase in amylase secretion from rat pancreatic fragments were 3 · 10-6, 10-7, 10-8, 3 · 10-6, and 3 · 10-6 M, respectively. The maximal concentration of vasoactive intestinal peptide tested (3 · 10-6 M) increased amylase secretion by 250%. The six secretagogues could be separated into two groups according to their effects on lipid metabolism and ATP levels. 2. 2. When used at their optimal concentrations, carbamylcholine, bombesin, pancreozymin, and pentagastrin lowered pancreatic ATP levels by 18-26% and increased net release of free fatty acids by 68-105%. 3. 3. The effects of 3 · 10-6 M carbamylcholine and 10-8 M pancreozymin on the metabolism of 3H2O, d-[U-14C]glucose and [1-14C]acetate were similar; the incorporation of radioactivity in the fatty acid moiety of glycerolipids decreased by 20-50% whereas the incorporation of 3H from 3H2O and of 14C from [U-14C]glucose increased by 20-35% in the glycerol moiety. In addition, the oxidation of [U-14C]glucose, [1-14C]acetate and [1-14C]palmitate to 14CO2 increased by 15-32% while the esterification of [1-14C]palmitate, [1-14C]-linoleate, and [1-14C]arachidonate was inhibited by 14-23%. The spectrum of fatty acids labeled with [1-14C]acetate indicated an inhibition of the malonic acid pathway whereas the elongation of polyenoic fatty acids was unaltered. 4. 4. The effects of carbamylcholine and pancreozymin on amylase secretion and lipid metabolism were markedly reduced in a Ca2+-free medium or in the presence of heavy water. 5. 5. Secretin and vasoactive intestinal peptide provoked none of the preceding effects even when tested at concentrations inducing a comparable rate of secretion. © 1979.