Hepatic Venous Plasma Research Articles

Neither adrenergic nor cholinergic antagonists in the central nervous system affect 2-deoxy- d-glucose(2-DG)-induced hyperglycemia

To investigate whether the brain adrenergic and cholinergic neurotransmitter systems are involved in the regulation of 2-deoxy- d-glucose (2-DG)-induced hyperglycemia, we studied the effects of adrenergic and cholinergic antagonists on 2-DG-induced secretion of epinephrine and glucagon, and hyperglycemia, in anesthetized fed rats. When 2-DG (10 mg/10 μl) was injected into the third cerebral ventricle, hepatic venous plasma glucose, glucagon, and epinephrine concentrations were significantly increased. Co-administration of phentolamine, propranolol, atropine and hexamethonium (1 × 10 −7 mol) with 2-DG did not modify the hyperglycemia responses normally observed after the administration of 2-DG alone. From this evidence we concluded that neither brain adrenoceptive nor cholinoceptive neurons are involved in the regulation of 2-DG-induced hyperglycemia.

Neostigmine-induced hyperglycemia is mediated by central muscarinic receptor in fed rats

We previously reported that neostigmine injected into the third cerebral ventricle stimulated adrenal secretion of epinephrine, secretion of glucagon from the pancreas, and direct neural innervation of the liver, resulting in hepatic venous plasma hyperglycemia in anesthetized fed rats. However, receptor type of these 3 mechanisms is not known. Therefore, we examined the effects of intraventricularly injected cholinergic or adrenergic antagonists on neostigmine-induced catecholamines in intact rats, glucagon secretion which is mediated by direct neural innervation of pancreas in bilateral adrenalectomized (ADX) rats, and hepatic venous hyperglycemia which is mediated by direct neural innervation of liver in ADX rats receiving constant infusion of somatostatin from femoral vein. Atropine injected into the third cerebral ventricle suppressed epinephrine secretion and dose-dependently inhibited hepatic venous hyperglycemia induced by neostigmine in intact rats. The neostigmine-induced glucagon secretion which occurs in ADX rats was suppressed by atropine. Atropine also prevented the neostigmine-induced hyperglycemia in ADX rats receiving constant somatostatin infusion through femoral vein (ADX-Somato rats). On the other hand, phentolamine, propranolol and hexamethonium showed no significant inhibitory effect on neostigmine-induced hyperglycemia, epinephrine and glucagon secretion in intact rats, glucagon secretion in ADX rats, or hyperglycemia in ADX-Somato rats. These results suggest that neostigmine-induced epinephrine and glucagon secretion and increased hepatic glucose output stimulated by direct neural innervation to liver is mediated by central muscarinic receptor in fed rats.

Central nervous system control of glycogenolysis and gluconeogenesis in fed and fasted rat liver

The influence of brain cholinergic activation on hepatic glycogenolysis and gluconeogenesis was studied in fed and 48-hour fasted rats. Neostigmine was injected into the third cerebral ventricle and hepatic venous plasma glucose, glucagon, insulin, and epinephrine were measured. The activity of hepatic phosphorylase-a and phosphoenolpyruvate-carboxykinase (PEP-CK) was also measured. Experimental groups: 1, intact rats; 2, rats infused with somatostatin through the femoral vein; 3, bilateral adrenodemedullated (ADMX) rats; 4, somatostatin infused ADMX rats; 5, 5-methoxyindole-2-carboxylic acid (MICA) was injected intraperitoneally 30 minutes before injection of neostigmine into the third cerebral ventricle of intact rats. MICA treatment completely suppressed the increase in hepatic glucose in fasted rats, but had no effect in fed rats. Phosphorylase-a activity was not changed in fasted rats, but increased in fed rats, intact rats, somatostatin-infused rats, somatostatin-infused ADMX rats, and ADMX rats in that order. PEP-CK was not changed in fed rats, but increased at 60 and 120 minutes after neostigmine injection into the third cerebral ventricle in fasted rats. We conclude that, in fed states, brain cholinergic activation causes glycogenolysis by epinephrine, glucagon, and direct neural innervation. In fasted states, on the other hand, gluconeogenesis is dependent on epinephrine alone to increase hepatic glucose output.

Vagally mediated insulin secretion by stimulation of brain cholinergic neurons with neostigmine in bilateral adrenalectomized rats

This study investigated the relationship between central cholinergic neurons and insulin secretion in bilateral adrenalectomized fed rats. Neostigmine (a cholinesterase inhibitor, 5 × 10 −8) mol admistered into the third cerebral ventricle produced significant increases in hepatic venous plasma insulin and glucose concentrations, whereas i.v. injection of the same dose of neostigmine did not. Prior acute subdiaphragmatic vagotomy or i.p. pre-injection with methylatropine (10 −8 mol) completely prevented the neostigmine-induced rise in plasma insulin concentration. Intraperitoneal pretreatment with hexamethonium (5 × 10 −8 mol) also significantly reduced the plasma insulin response. These peripheral pretreatments did not change the plasma glucose response to neostigmine. Intraventricular co-administration of 10 −9 mol methylatropine, a dose that was ineffective when pre-injected i.p., eliminated the plasma insulin and glucose responses to neostigmine, whereas hexamethonium (5 × 10 −8 mol) had no influence on either response to neostigmine. These observations suggest that stimulation of central cholinergic-muscarinic neurons with third cerebral ventricular injection of neostigmine results in vagally mediated insulin secretion in bilateral adrenalectomized fed rats.

Involvement of the Hippocampus in Central Nervous System-Mediated Glucoregulation in Rats

To find out whether the hippocampus is involved in central nervous system-mediated glucoregulation, we injected saline, neostigmine, dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, and prostaglandin F2 alpha into the dorsal hippocampus in anesthetized fed rats. After injection of dopamine, norepinephrine, bombesin, beta-endorphin, somatostatin, or prostaglandin F2 alpha, the level of hepatic venous plasma glucose did not differ from that in saline-treated control rats. However, neostigmine, an inhibitor of acetylcholine esterase, caused a dose-dependent increase in the hepatic venous plasma glucose concentration. This neostigmine-induced hyperglycemia was dose-dependently suppressed by coadministration of atropine, but not by hexamethonium. Injection of neostigmine (5 X 10(-8) mol) resulted in an increase not only in glucose but also in glucagon, epinephrine, and norepinephrine in hepatic venous plasma. In bilateral adrenalectomized rats, neostigmine-induced hyperglycemia was suppressed, but the hepatic venous plasma glucose concentration still increased significantly. These results indicate that the hippocampus is involved in central nervous system-mediated glucoregulation through cholinergic muscarinic activation, partly via epinephrine secretion.

The Relative Importance of Nervous System and Hormones to the 2-Deoxy-D-Glucose-Induced Hyperglycemia in Fed Rats

We examined the relative contributions of hormones and nervous system to the total 2-deoxy-D-glucose (2-DG)-induced central nervous system-mediated hyperglycemia. 2-DG was injected into the third cerebral ventricle in the following four groups of rats, and hepatic venous plasma glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were measured: 1) intact rats; 2) intact rats receiving somatostatin with insulin infusion through the femoral vein to inhibit glucagon secretion and maintain the basal insulin level; 3) bilateral adrenalectomized (ADX) rats to prevent epinephrine secretion; and 4) ADX rats receiving somatostatin with insulin infusion. Comparing areas under glucose curves among the intact rats, those receiving somatostatin with insulin infusion, ADX rats, and ADX rats receiving somatostatin with insulin infusion, the area under the glucose curve was intact rats greater than intact rats receiving somatostatin with insulin infusion greater than ADX rats receiving somatostatin with insulin infusion greater than ADX rats. These results suggest that there are three distinct sympathetic nervous system responses to 2-DG-induced central nervous system-mediated hyperglycemia. 2-DG-induced hyperglycemia is not dependent on only one of those three systems, it is dependent on all of them. The relative potency of the factors to 2-DG-induced hyperglycemia increases in the following order: direct neural innervation of liver (including suppressive epinephrine action on insulin secretion), glucagon, and direct epinephrine action on liver.

Pharmacokinetics and metabolism of neurotensin in man.

We studied the pharmacokinetics, arteriovenous extraction, and degradation sites of neurotensin (NT) in man during iv infusions of synthetic intact NT [NT-(1-13)] and the NH2-terminal metabolite NT-(1-8) during lipid ingestion and by catheterization of various vascular beds in normal subjects and patients with hepatic disease. NT-like immunoreactivities in plasma were quantitated using 2 sequence-specific RIAs and gel filtration chromatography. During iv infusion of NT-(1-13) in 6 normal subjects, the median t1/2 was 1.7 min (interquartile range, 0.7-2.8), the MCR was 36 mL/kg.min (range, 21-54), and distribution space was 78.8 mL/kg (range, 56-91). The results were similar at infusion rates of 72, 144, and 288 pmol/kg.h (n = 6). During infusion of NT-(1-8) in 7 normal subjects, the median t1/2 was 8.3 min (range, 4.7-13.8), the MCR was 11.0 mL/kg.min (range, 6.7-21.7), and the distribution space was 142.6 mL/kg (range, 45.3-281.0). Significant peripheral arteriovenous extraction of NT-(1-13) was found at infusion rates of 144 and 288 pmol/kg.h. Extraction of NH2-terminal immunoreactivity was not significant. Intact NT was identified by gel chromatography in arterial plasma after lipid ingestion and iv infusion of NT-(1-13), but postprandially in only low concentrations. In 17 patients with various nonhepatic diseases, plasma intact NT levels were not different in blood sampled from the renal vein, inferior vena cava, brachial artery, or hepatic vein. In contrast, NH2-terminal immunoreactivity was significantly higher in hepatic venous than in systemic plasma. In 6 patients with hepatic disease, systemic plasma intact NT levels were increased, but even more so in hepatic venous plasma. These results demonstrate that metabolism of intact NT is rapid, and a significant peripheral arterio-venous extraction is present. Further studies are necessary to establish if the liver is a site of degradation of intact NT in man.

Relative contributions of the nervous system and hormones to CNS-mediated hyperglycemia.

We quantitatively determined the relative contributions of hormonal factors and the nervous system to the total glucose response after stimulation of the cholinergic neurons in the central nervous system of fed rats. Hepatic venous plasma glucose, glucagon, insulin, epinephrine, and norepinephrine were measured during 120 min after injection of neostigmine (5 X 10(-8) mol) into the third cerebral ventricle in rats subjected to bilateral adrenodemedullation (ADMX) to prevent epinephrine secretion (observed insulin secretion), with and without intravenous infusion of somatostatin to prevent glucagon and insulin secretion. Injection of neostigmine in intact rats resulted in increases in glucose, glucagon, epinephrine, and norepinephrine. Comparison of glucose areas suggests that 22% of the hyperglycemic response is due to the glucagon effect, that 29% is due to the epinephrine effect, and that an unknown factor other than epinephrine or glucagon, which may include activation through direct neural innervation of the liver via alpha-adrenergic receptor, contributes 49%. The suppressive effect of epinephrine on insulin secretion, which is potentially stimulated by direct neural activation of the pancreas, contributes 18% of the net hyperglycemia.

Hypocholesterolaemic Effects of Dietary Propionate: Studies in Whole Animals and Perfused Rat Liver

In adult male rats fed a non-purified diet supplemented with 5% sodium propionate, plasma cholesterol concentrations were significantly depressed. Although liver cholesterol was increased by feeding propionate, rates of hepatic cholesterol and fatty acid synthesis were unchanged. Tissue concentrations and rates of synthesis of cholesterol were also unaffected by dietary propionate in stomach, small intestine and caecum. Concentrations of propionate in hepatic portal venous plasma were raised by feeding the supplemented diet but the increase was low in comparison to the dietary intake. Examination of the gut contents revealed concentrations of total volatile fatty acids (VFA) of 19 mumol/ml in the stomach contents of control rats and 148 mumol/ml (of which propionate contributed 116 mumol/ml) in those fed the supplemented diet. Duodenal and ileal concentrations of VFA were very low and were only slightly raised in the propionate-fed rats while caecal VFA were the same in both groups with a combined mean of 159 mumol/ml. These data indicate that in the rat, the absorption of dietary propionate appears to occur in the stomach. In pigs fed a standard ration hepatic portal venous VFA remained low for the first 4 h after feeding but then rose with the onset of large bowel fermentation. Feeding the diet supplemented with propionate caused hepatic portal venous plasma concentrations to rise by approximately 0.4 mumol/ml. This increase was apparent 30 min after feeding and was sustained for 3 h but subsequently there was no difference to controls. As in the rat, the absorption of dietary propionate appeared to occur in the upper gastrointestinal tract. The transport of propionate via the porcine hepatic portal vein also appeared insufficient to account for the dietary intake and suggests metabolism of the acid by the upper gastrointestinal tract. Further studies with perfused livers from fed rats indicated that propionate at a concentration of 1 mumol/ml did not alter cholesterol synthesis but that inhibition occurred at 18 mumol of propionate/ml. It appears that a redistribution of cholesterol from the plasma to the liver, rather than inhibition of hepatic and intestinal cholesterol synthesis, is responsible for the hypocholesterolaemic effects of dietary propionate. Because the absorption and transport of dietary propionate appears to follow a time course which differs considerably to that of the acid produced by the large bowel microflora, we conclude also that VFA produced by such fermentation would not seem to be responsible for the hypocholesterolaemic effects of certain water-soluble plant fibres.

A viscous fibre (methylcellulose) lowers blood glucose and plasma triacylglycerols and increases liver glycogen independently of volatile fatty acid production in the rat.

1. Adult male rats were maintained on diets containing 80 g methylcellulose/kg of low (25 cP), medium (400 cP) and high (1500 cP) viscosity. 2. After 10 d, the viscosity of stomach and caecal contents was found to have increased in proportion to that of the dietary fibre. Concentrations of volatile fatty acids in caecal digesta were lowest with the high-viscosity fibre but acetate was the major acid present with all three diets. Acetate was the only acid found in significant quantities in hepatic portal venous plasma and concentrations of this acid were unaffected by diet. 3. Concentrations of glucose in arterial blood were low with the medium- and high-viscosity diets while the content of liver glycogen was high. These effects of fibre were not directly on glucose absorption as the intestines were net removers of the hexose at the time of sampling. 4. Hepatic lipogenesis and plasma triacylglycerol concentrations were both higher in rats fed on the low-viscosity fibre. Plasma cholesterol concentrations, hepatic cholesterol synthesis and faecal bile acid excretion were not altered by dietary fibre viscosity. 5. We conclude that the effects of dietary fibre on carbohydrate absorption and storage and fatty acid synthesis are a function of the viscosity of the fibre in solution, high viscosity slowing the digestion and absorption of nutrients in the small intestine. Large-bowel microbial fermentation is not of direct significance to these events. In contrast, effects of fibre polysaccharides on sterol metabolism seem not to be related to their rheological properties.

Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats

Central versus peripheral effect of clonidine on hepatic venous plasma glucose concentrations in fasted rats

Improved high-performance liquid chromatographic assay for the quantification of 5-bromo-2′-deoxyuridine and 5-bromouracil in plasma

A sensitive and specific procedure using high-performance liquid chromatography (HPLC) was developed for the quantification of 5-bromo-2′-deoxyuridine (BUdR) and 5-bromouracil (BU) in plasma. BUdR and BU were first extracted with a mixture of ethyl acetate and 2-propanol from plasma presaturated with solid ammonium sulfate. Following evaporation of the organic extract, the remaining residue was reconstituted in saturated ammonium sulfate solution, washed with a mixture of n-pentane—methylene chloride and re-extracted with the original solvent mixture. The organic extract was evaporated, reconstituted in mobile phase and chromatographed on a regular-bore ODS HPLC column using ultraviolet absorbance detection. The BUdR and BU quantification limits were both 0.1 μ M, the mean intra-assay coefficients of variation were 5.0 and 5.6%, respectively, and the mean inter-assay coefficients of variation were 5.4 and 10.7%, respectively. This method was used to determine steady-state femoral arterial and hepatic venous plasma concentrations of BUdR and BU in a patient receiving a continuous intravenous infusion of BUdR (20 mg/kg per day).

Effects of naloxone on glucose level in the hepatic venous plasma in the rat.

1. The effect of opioid receptor blockade by naloxone in vivo on hepatic venous plasma glucose concentration in rats was investigated. 2. The plasma glucose levels in naloxone-injected animals (10 mg/kg) were higher than in the control animals (P less than 0.05). 3. At the lower dose of naloxone (2 mg/kg) the resulting plasma glucose concentration did not differ significantly from control (P greater than 0.1). 4. It is concluded that endogenous opioids may moderate the regulation of basal glucose levels in the rat.

Gut-liver interaction in glutamine homeostasis: portal ammonia role in uptake and metabolism.

The role of ammonia released by the gut on hepatic glutamine handling and metabolism was studied in postabsorptive anesthesized male Sprague-Dawley rats at spontaneous and elevated arterial glutamine concentrations. Glutamine handling and metabolite release across both organ beds were studied using arteriovenous concentration differences and simultaneously measured portal and hepatic venous plasma flows. At the spontaneous arterial glutamine load, fractional glutamine extraction, FE-Gln, by the gut and the liver was 24 and 10%, respectively. At the elevated glutamine load, gut glutamine uptake doubled, while FE-Gln remained at 24%; however, portal ammonia and alanine increased and decreased, respectively. In response, hepatic FE-Gln increased to 28% with a large release of glutamate and urea. The role of portal ammonia in modulating hepatic glutamine uptake was studied by infusing NH4HCO3 directly into the portal vein. Increasing the portal load promptly stimulated hepatic glutamine uptake and glutamate and urea release. Mitochondria isolated from these livers produced more glutamate from glutamine, suggesting ammonia activation of hepatic glutaminase flux; in addition, citrulline formation increased, suggesting a coupling of glutaminase flux to urea synthesis. The results are consistent with portal ammonia release acting as a key informational molecule in interorgan glutamine flow.

Mechanism of central hyperglycemic effect of cholinergic agonists in fasted rats.

The influence of cholinergic agonists on central nervous system (CNS) regulation of blood sugar homeostasis was studied in fasted rats. When carbachol, muscarine, bethanechol, methacholine, or neostigmine was injected into the third cerebral ventricle, it caused a dose-dependent increase in the hepatic venous plasma glucose concentration. However, in the case of 1,1-dimethylphenyl-4-piperazinium iodide (DMPP) or nicotine, the level of hepatic venous glucose did not differ from that of the saline-treated control rats. The increase in glucose level caused by neostigmine was dose-dependently suppressed by coadministration of atropine. These facts suggest that cholinergic activation of muscarinic receptors in the CNS plays a role in increasing hepatic glucose output. Injection of neostigmine (5 X 10(-8) mol), an inhibitor of cholinesterase, into the ventricle resulted in the increase of not only glucose, but also glucagon, epinephrine, and norepinephrine in the hepatic venous plasma. However, constant infusion of somatostatin through a femoral vein completely prevented the increase of glucagon after administration of neostigmine, although the increase of hepatic venous glucose and epinephrine levels were still observed. Neostigmine-induced increments in glucose did not occur in adrenalectomized rats. This suggests that the secreted epinephrine acts directly on the liver to increase hepatic glucose output.

Effects of Food Restriction and Starvation-Refeeding on Volatile Fatty Acid Concentrations in the Rat

Adult male rats were fed either ad libitum or at levels of 19 or 15 g of nonpurified diet per rat daily or subjected to 48 h of starvation followed by 24 h of refeeding. Concentrations of total and individual volatile fatty acids (VFA) in cecal contents were higher in rats fed ad libitum than in those restricted to 19 or 15 g/d. Only butyrate concentration was lower in rats given 15 g/d than in those given 19 g/d. In starved animals all cecal VFA declined within 24 h of food removal, but the greatest change was in butyrate, which fell to less than 12% of the initial value. Acetate and propionate fell further after 48 h, but their concentrations were restored to control values within 24 h of refeeding while butyrate remained depressed by 50%. Cecal pH was closely related to total VFA concentration, although the highest degree of correlation was with butyrate. Hepatic portal venous plasma VFA concentrations generally reflected those in cecal digesta except that the proportion of butyrate was relatively lower in this blood vessel than in cecal contents. Under all conditions acetate was the only VFA found in arterial plasma and in the fully fed state was lower than in hepatic portal venous plasma. Food restriction and starvation did not alter arterial concentrations, indicating abolition of net uptake. We conclude that all VFA are affected by availability of fermentable material to the large bowel microflora but that the disproportionate changes in butyrate may reflect preferential use of this acid by cells of the large bowel wall.

Increase in plasma glucose concentration after intracerebroventricular injection of N,O'-dibutyryl cyclic adenosine 3',5'-monophosphate.

The effect of chemical stimulation of the central nervous system was studied in anesthetized rats. (Bu)2 cAMP, cAMP, 5'-adenosine monophosphate (AMP), ATP, and (Bu)2 N6,O2-dibutyryl guanosine-3'5'-cyclic monophosphate sodium salt were injected directly into the third cerebral ventricle, and changes in hepatic venous plasma glucose, immunoreactive glucagon, and insulin concentrations were studied. The injection of (Bu)2cAMP (1 X 10(-8) to 5 X 10(-7) mol/microliter saline) into the third cerebral ventricle caused a dose-dependent hyperglycemia associated with increased immunoreactive glucagon. (Bu)2cAMP-induced hyperglycemia and hyperglucagonemia were inhibited by prior bilateral adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with (Bu)2cAMP (5 X 10(-7) mol) into the third cerebral ventricle abolished both (Bu)2cAMP-induced hyperglycemia and an increase of glucagon secretion. These results suggest that cAMP may act intracellularly within the central nervous system to increase hepatic glucose output, and this appears to depend on the adrenal gland. Epinephrine secreted from the adrenal gland may directly act on the liver or enhance glucagon secretion, which in turn increases hepatic glucose output.

Effect of Infusion of Salmon Calcitonin on the Secretion of Somatostatin and Gastrin in Man

In vitro and animal studies have pointed out complex interrelations between gastrointestinal hormones and calcitonin. To analyse the acute effects of calcitonin in more detail, patients undergoing surgery were infused intravenously with synthetic salmon calcitonin, a potent analog of the human hormone. Samples were taken after 0, 30 and 60 minutes from the hepatic, portal and a peripheral vein. Somatostatin and gastrin were determined by radioimmunoassay. The mean basal levels of somatostatin in peripheral and hepatic venous plasma (14.2 and 15.6 pg/ml) were significantly lower than in portal plasma (45.6 pg/ml), indicating effective removal by the liver. After infusion of calcitonin there was a general rise in somatostatin levels and an increase in the gradient between hepatic and portal blood. Basal gastrin levels were highest in the portal vein when compared intraindividually. The differences disappeared after calcitonin infusion with a concomitant systemic reduction of gastrin levels. Thus, calcitonin is able to stimulate the secretion of somatostatin from the gastrointestinal tract and does reduce gastrin secretion, possibly via the stimulation of somatostatin secretion.

Central hyperglycaemic effect of adrenaline and carbachol.

The effect of chemical stimulation of the brain on glucoregulation was studied in anaesthetized rats. Adrenaline, noradrenaline, acetylcholine, dopamine and carbachol (5 X 10(-8) mol/microliter saline) were injected directly into the third cerebral ventricle and changes in hepatic venous plasma glucose, immunoreactive glucagon and insulin concentrations were studied. The injection of adrenaline and carbachol into the third cerebral ventricle resulted in a marked hyperglycaemia associated with increased immunoreactive glucagon. Adrenaline-induced hyperglycaemia was not affected by bilateral adrenalectomy, while carbachol-induced hyperglycaemia was completely inhibited by adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with adrenaline into the third cerebral ventricle did not influence adrenaline-induced hyperglycaemia, while carbachol-induced hyperglycaemia was inhibited by co-administration with somatostatin. These results suggest that adrenergic and cholinergic neurons in the central nervous system may increase hepatic glucose output by different mechanism.

Plasma and caecal volatile fatty acids in male and female rats: Effects of dietary gum arabic and cellulose

Adult male and female rats were fed synthetic diets containing 10% gum arabic or cellulose. Concentrations of total volatile fatty acids in caecal fluid and hepatic portal venous plasma of both sexes were higher on the gum arabic diet. Total and individual acids in caecal fluid did not differ between male and female rats fed gum arabic, but with cellulose concentrations of acetate and propionate were significantly lower in females than in males. Caecal pH correlated negatively with volatile fatty acid concentration in both sexes, but with gum arabic, pH was significantly lower in males than in females with the same caecal volatile fatty acid concentration. The concentration and distribution of plasma volatile fatty acids in the hepatic portal vein generally reflected that of caecal fluid although acetate concentrations were lower in male than in female rats fed gum arabic. Blood glucose and plasma triacylglycerols were unrelated to hepatic portal venous plasma volatile fatty acids but in males liver glycogen in each dietary group was positively correlated with volatile fatty acid concentration. This relationship was absent in females. It is concluded that there are differences in the production and absorption of volatile fatty acids between male and female rats and that these are affected by the source of dietary fibre.