In vitro lipid metabolism in the rat pancreas II. Effects of secretagogues on fatty acid metabolism, net lipolysis and ATP levels

Abstract

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. 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. 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.

Non-Oxidative Metabolism of Ethanol by Rat Pancreatic Acini

“…With respect to the pancreas, acetaldehyde is associated with pancreatic tissue injury in experimental animals [34,35] and inhibits amylase secretion from isolated pancreatic acini [36,37]. Acetate can serve as a substrate for fatty acid synthesis in the pancreas [19]. A redox change following ethanol administration has been reported in the pancreas (reduced [NAD + ]/[NADH] [H + ] ratio and increased lactate/pyruvate ratio) that is qualitatively similar to that occurring in the liver [38].…”

“…However, when 14 C-ethanol is oxidized to acetate within the pancreas [4], the resulting 14 C-acetate can also be incorporated into 14 C-fatty acids [19]. The validity of assuming that the ethanol moiety of the FAEE carries the bulk of the radiolabel was tested by a saponification procedure which hydrolyses the ester bond of FAEEs to yield ethanol and fatty acid.…”

In vitro effects of ethanol and ethanol metabolism in the rat pancreas

“…Ethanol exerted no effect on basai amylase sécrétion for at least 1 h when tested in the 0.5-200 mM concentration range. The 4-fold increase of basai sécrétion evoked by a 3* 10"^ M optimal concentration of carbamylcholine [7] was also unaffected by ethanol (data not shown).…”

“…In rat, lipid inclusions are also observed in pancreatic acinar cells after a few days of ethanol administration [4,5]. Taking advantage of a récent study of in vitro lipid metabolism in the rat pancréas [6][7][8], we decided to investigate the effects of ethanol on the intermediate metabolism of this gland. Such direct in vitro effects have not yet been documented, except in a few préliminary studies [9].…”

In vitro lipid metabolism in the rat pancreas III. Effects of carbamylcholine and pancreozymin on the turnover of phosphatidylinositols, 1,2-diacylglycerols and phosphatidylcholines

“…0.11 MM Na2H''P04 (625 Ci/mol), 0.5 mM myo-[2-'H]inositol (36 Ci/mol) and 0.5 mM [Me-'''C]choline chloride (5 Ci/mol) were also used. Incubation conditions, lipid extraction and analysis were the same as in the previous papers [4,5].…”