Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “OLEIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,765 records · Page 98Linked to original sources
PubMed1990

Sampling of lung interstitial fluid in intact dog.

This paper reports a method of sampling fluid from the peribronchial-perivascular space (PBVS) of the lungs in intact closed chest dogs. The PBVS was sampled by introducing a wick catheter into the PBVS through a mediastinoscope. The right lymph duct was cannulated by the method of Vriem and Ohkuda [J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 54: 199, 1983] for collection of lymph to compare to peribronchial fluid. The colloid osmotic pressure (COP) of PVBS and right lymph duct fluid (RLDF) were compared in a series of dogs infused with lactated Ringer's solution (LR) and lactated Ringer's combined with three other conditions: left atrial balloon inflation (LRB), oleic acid infusion (LRO), and oleic acid infusion and left atrial balloon inflation (LROB). Prior to LR infusion, the volume of samples of fluid from the PBVS wicks was inadequate for measuring COP (less than 4 microliters). This difference was significantly only in the later samples at 3, 4, and 5 hr in the LR and LRB groups. In the LRO and LROB groups, protein content and amount of fluid sampled were greater than in the LR and LRB groups, but the mean COPs of the wick PBVS and RLDF were not significantly different. This method of directly sampling interstitial fluid from the lungs of dogs without thoracotomy confirms the high COP of fluid from the lung interstitium. This method of PBVS fluid sampling is potentially feasible in a human patient undergoing mediastinoscopy.

Animals↗
PubMed2006

Optimisation of culture conditions with respect to biotin requirement for the production of recombinant avidin in Pichia pastoris.

Due to its very high affinity to biotin, avidin is one of the most widely exploited proteins in modern biotechnological and biomedical applications. Since biotin is an essential vitamin for the growth of many microorganisms, we examined the effect of biotin deficiency on growth for a recombinant Pichia pastoris strain expressing and secreting a recombinant glycosylated avidin. The results showed that biotin deficiency lowers growth rate and biomass yield for P. pastoris. Substitution of biotin in the medium by the two structurally unrelated compounds, aspartic acid and oleic acid, which do not bind to recombinant avidin was analyzed quantitatively. These two compounds had a growth promoting effect in biotin-deficient medium, but did not replace biotin completely. Indeed, in chemostat culture, wash-out occurred after about six liquid residence times and recombinant avidin productivity was lowered. However, addition of low amounts of biotin (20 microg L(-1) of biotin for a cell density of 8 g L(-1)) resulted in stable chemostat cultures on methanol with the production of recombinant biotin-free avidin. The specific avidin production rate was 22 microg g(-1) h(-1) at a dilution rate of 0.06 h(-1).

Aspartic Acid↗
PubMed1987

Metabolism of neutral lipids in cultured fibroblasts from multisystemic (or type 3) lipid storage myopathy.

The lipid metabolism in cultured fibroblasts from multisystemic (type 3) lipid storage myopathy (MLSM) and controls has been studied through pulse-chase experiments using radiolabelled oleic acid and acetate precursors. The uptake of radiolabelled oleic acid by MLSM fibroblasts was slightly higher than in controls but did not seem to be the primary defect of the multisystemic lipid storage myopathy. The uptake of radiolabelled acetate was quite similar in MLSM and in control cells. During short-time pulse periods, using either radiolabelled oleic acid or acetate as precursors, we observed no significant difference in lipid composition between MLSM and controls. In contrast, pulse experiments using radiolabelled oleic acid as precursor showed a major accumulation of radiolabelled triacylglycerols in MLSM (around 1000% of controls); no significant increase of other neutral or polar lipids was noticed. A similar triacylglycerol storage was observed by using radiolabelled acetate as precursor, but in this case the difference between MLSM and controls was more pronounced; we also observed in MLSM cells a higher amount of polar lipids which can be due to an increased rate of fatty acid biosynthesis (from radiolabelled acetate). Chase experiments, after pulse by low concentration of exogenous radiolabelled oleic acid or acetate, showed similar features: the biosynthesized triacylglycerols were not at all degraded in MLSM, but on the contrary increased, probably by accumulation of radiolabelled triacylglycerols newly synthesized from radiolabelled fatty acids liberated during the phospholipid turnover. Similarly, the triacylglycerol storage induced by high doses of fatty acids was not degraded in MLSM cells, in contrast to control cells. This suggested that the triacylglycerols synthesized in the presence of low and high levels of fatty acids were accumulated in only one subcellular cytoplasmic compartment without relationship with the lysosomal compartment, since these cells were not deficient in acid lysosomal lipase. The more probable hypothesis is a deficiency of the cytoplasmic catabolism of triacylglycerols in MLSM cells.

Acetates↗
PubMed1990

Characterization of FadL-specific fatty acid binding in Escherichia coli.

The product of the fadL gene (FadL) is a central component of the long-chain fatty acid transport system of Escherichia coli. When fatty acid activation is blocked by a mutation in the structural gene for acyl CoA synthetase (fadD) transport is inhibited allowing a FadL-specific fatty acid binding activity to be measured. This binding activity was 4- to 6-fold greater in the fadL+ fadD strain LS6928 when compared to the delta fadLfadD strain LS6929. With long-chain fatty acids, this binding activity was saturable and it was estimated that there were approx. 35,000 FadL-specific oleic acid binding sites per cell in the fadL+ strain LS6928. The FadL-specific fatty acid binding affinity was highest for oleic acid (18:1) and palmitic acid (16:0) giving apparent KD values of 2.3.10(-7) M and 8.8.10(-7) M, respectively. FadL-specific binding affinity of myristic acid (14:0) was nearly an order of magnitude less and no FadL-specific binding of decanoic acid (10:0) could be measured. Two lines of evidence suggest that FadL-fatty acid binding occurs by a hydrophobic interaction: (1) There was a preference for the long-chain substrates oleic acid and palmitic acid; and (2) oleic acid binding activity was not significantly changed over the pH range 5.0 to 8.0. The FadL-specific binding of oleic acid in the fadL+ strain LS6928 could be blocked by preincubation with antisera raised against purified FadL providing a clear correlation between the activity and identity of FadL. The binding activity associated with FadL was measured in vesicles of the outer membrane following passage over the hydrophobic resin Lipidex 1000. The KD of oleic acid binding attributable to FadL in outer membranes vesicles (6.0.10(-7) M) was in close agreement with that determined in whole cells. Overall, these studies demonstrated that FadL binds long-chain fatty acids with a relatively high affinity prior to their transport across the outer membrane.

Bacterial Outer Membrane Proteins↗
PubMed1993

Adaptive cytoprotection in the small intestine: role of mucus.

Gastric mucosal injury induced by strong irritants can be dramatically reduced by pretreating the mucosa with mild forms of the same irritant. This phenomenon has been termed "adaptive cytoprotection." The aim of the present study was to use in vivo and in vitro approaches to study adaptive cytoprotection in the small intestine using physiologically relevant concentrations of oleic acid. Anesthetized rats were instrumented for perfusion of the proximal jejunum with 10 or 40 mM oleic acid (in 20 mM sodium taurocholate). Mucosal epithelial integrity was continuously monitored by measuring the blood-to-lumen clearance of 51Cr-labeled EDTA. Perfusion of the lumen with 40 mM oleic acid produced a 10-fold increase in 51Cr-EDTA clearance, which was not affected by a previous perfusion with 10 mM oleic acid, i.e., no adaptive cytoprotection. In another series of experiments, oleic acid was placed in the lumen rather than perfused, and mucosal epithelial integrity was assessed histologically. Intraluminal placement of 10 mM oleic acid resulted in the generation of a mucus layer over the epithelium. Subsequent placement of 40 mM oleic acid did not produce significant epithelial cell injury, i.e., adaptive cytoprotection. In in vitro studies, mucin (1, 5, and 10 mg/ml) was layered over confluent monolayers of Caco-2 cells prior to addition of 2 mM oleic acid in 4 mM sodium taurocholate. The epithelial cell injury induced by oleic acid was inhibited by mucin in a dose-dependent manner. Further studies indicate that mucin does not prevent, but simply delays, the onset of cell injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Acclimatization↗
PubMed2003

The effect of supplementing layer diets with shark cartilage or chitosan on egg components and yolk lipids.

1. An experiment was designed to evaluate the effects of the addition of shark cartilage (SC) or chitosan (CH) to layer diets on egg component weights, yolk lipids and hen plasma lipids. 2. Hy-Line laying hens (80) were used during a 56 d feeding trial. Treatments were: basal diet (BD), BD + 20 g/kg SC, BD + 30 g/kg SC, BD + 20 g/kg CH and BD + 30 g/kg CH. Eggs were analysed on d 14, 28, 42 and 56. 3. Egg weight and egg component weights were not affected by these treatments throughout the experimental period. 4. After 14d of experimental feeding, cholesterol levels were higher in eggs from birds given BD + 20 g/kg CH and BD + 30 g/kg CH than in those from birds given BD. 5. Furthermore, eggs from hens given BD + 20 g/kg SC or BD + 20 g/kg CH were higher in palmitic and stearic acids and lower in oleic acid than those from birds fed on BD. After 56 d feeding, however, palmitic and stearic acid contents in eggs from hens given any of the supplemented diets were lower than in those from hens given BD, and oleic acid in eggs from hens given BD + 20 g/kg SC, BD + 30 g/kg SC and BD + 30 g/kg CH was higher than in those from birds fed on BD. 6. Plasma cholesterol and triacylglycerol levels were not significantly affected by dietary treatment. 7. Shark cartilage or chitosan at up to 30 g/kg in layer diets did not affect egg component weights (yolk, white and shell) and total lipid contents. During the period from 42 to 56d of experimental feeding, diets containing up to 30 g/kg chitosan reduced egg yolk contents of cholesterol, palmitic and stearic acids and increased the content of oleic acid.

Animal Feed↗
PubMed1977

Evidence for participation of cytochrome b5 in microsomal delta-6 desaturation of fatty acids.

The delta-6 desaturation of linoleic acid to gamma-linolenic acid and oleic acid to 6,9-octadecadienoic acid by rat liver microsomes was investigated. Using a specific antibody prepared against purified rat liver cytochrome b5, we demonstrated that cytochrome b5 participated in delta-6 desaturation of both fatty acids. The reaction products were identified as their methyl ester derivatives by argentation thin-layer chromatography, gas-liquid chromatography, and reductive ozonolysis followed by gas-liquid chromatography.

Animals↗
PubMed2005

Dietary protein:lipid ratio and lipid nature affects fatty acid absorption and metabolism in a teleost larva.

Studies with teleost larvae have reported poor performance associated with quantitative lipid imbalances in the diet. The present study examined the effect of dietary protein:neutral lipid ratio on fatty acid (FA) absorption efficiency and metabolism in larval Senegalese sole. In addition, the effect of lipid class (triolein (TRI) and l-3-phosphatidylcholine-1,2-di-oleoyl (PC)), carbon number and degree of saturation of the labelled NEFA, stearic acid (SA), oleic acid (OA) and DHA) was tested. FA absorption was determined by tube feeding [1-14C]-labelled lipids and NEFA after a single meal of either non-enriched Artemia (NEA) or Artemia enriched on a soyabean oil emulsion (EA), or after feeding these diets over an extended period of time (18 d). The tested dietary protein:lipid ratios had no short-term influence but long-term feeding of a diet higher in neutral lipid (EA) increased lipid accumulation within the gut epithelium and resulted in lower FA absorption (higher label evacuation and lower retention of dietary FA), which may partially explain the trend for lower growth observed with this diet. The lipids and NEFA, showed different digestive and metabolic properties, independent of feeding regime. FA absorption increased with unsaturation, being lowest for SA, followed by OA, and highest for DHA. In addition, sole larvae had a lower capacity to digest and absorb FA esterified to TRI, compared with PC, with the order of decreasing absorption being NEFA>PC>>TRI. Moreover, larvae appeared to discriminate between the source of OA, as this FA in the free form or esterified to PC was catabolised less than TRI.

Absorption↗
PubMed2004

Differential effects of dietary fatty acids on the regulation of CYP2E1 and protein kinase C in human hepatoma HepG2 cells.

We investigated the effects of different fatty acids (FAs) or with different degrees of unsaturation on cytochrome P450 2E1 (CYP2E1) induction and protein kinase C (PKC) activity in human hepatoma HepG2 cells. As the degree of unsaturation increased, the cell survival rate decreased for FAs with 18 carbons, but linolenic acid (LNA) or docosahexaenoic acid (DHA) groups were similar even through they have different degrees of unsaturation. Treatment with palmitic acid (PA), oleic acid (OA), linoleic acid (LA), LNA, and DHA resulted in respective cellular FA concentrations of C16:0 (43.1%), C18:1 (18.5%), C18:2 (7.4%), LNA (2.85%), and C22:6 (3.13%), which was highest for the FA that was used as the treatment, indicating that their incorporation within the cell is directly proportional to treatment. After 2 hours of cultivation, the lipid peroxide (LPO) in the DHA group increased 600% compared with control, and was much higher than in the groups treated with the other FAs, with LNA > LA > OA > PA. CYP2E1 induction increased with greater effect as the degree of unsaturation of OA, LA, and DHA increased. PA did not affect PKC activity, but DHA treatment increased PKC activity the most. The effects of LNA and LA were similar, but less than that of DHA, and that of OA was lower still, indicating that activity of PKC is proportional to the degree of unsaturation, and not the configuration of the FA. Increased plasma membrane concentrations of n-3 FA, such as DHA, might exert regulatory effects on PKC by increasing membrane fluidity, causing changes in CYP2E1, elevating levels of LPO, or producing oxidative stress.

Carcinoma, Hepatocellular↗
PubMed1996

Long-term effects of participation in a randomized trial of a low-fat, high-carbohydrate diet.

In 1982 we started a series of pilot studies to examine the feasibility of dietary intervention with a low-fat, high-carbohydrate diet in women with extensive mammographic densities. The purpose of the present paper is to examine the long-term effects of participation in these studies by assessing nutrient intake and other variables several years after active participation had stopped. Two hundred sixteen women were eligible for the follow-up study and were invited to attend and interview with a dietician. Data were collected by food frequency questionnaire from 157 subjects (73%), and blood was obtained from 115 subjects. Total energy intake was slightly lower in the intervention group. Total fat and percent energy from fat were significantly lower in the intervention group. The intake of all types of fat (saturated fat, linoleic acid, and oleic acid) and dietary cholesterol was lower in the in the intervention group; however, the polyunsaturated/saturated fat ratio did not differ between the groups. Total cholesterol and apoprotein B levels were lower in the intervention group compared to the control group. Follicle-stimulating hormone was 29% higher in postmenopausal members of the intervention group than in controls, but there was no difference in levels of estradiol. A total of 19 women enrolled in pilot studies had developed breast cancer, 5.7 times the number expected, confirming that the selection of women with extensive mammographic densities does identify a high-risk group. These data suggest that even quite short periods of intensive dietary counselling may have prolonged effects on diet, and that once subjects have adopted new dietary habits, the habits may persist even in the absence of continued counselling.

Adult↗
PubMed2006

Thermosensitive Y-shaped micelles of poly(oleic acid-Y-N-isopropylacrylamide) for drug delivery.

A novel thermosensitive amphiphilic copolymer comprised of two hydrophobic poly(oleic acid) (POA) segments and one hydrophilic poly(N-isopropylacrylamide) (PNIPAAm) segment was designed and synthesized. The structure of the copolymer was confirmed as Y-shaped by FTIR, 1H NMR, and SEC-MALLS analysis. A cytotoxicity study shows that the P(OA-Y-NIPAAm) copolymer exhibits good biocompatibility. The copolymer may self-assemble into micelles in water, with the hydrophobic POA segments at the cores of micelles and the hydrophilic PNIPAAm segments as the outer shells. The resulting micelles demonstrate temperature sensitivity with a lower critical solution temperature (LCST) of 31.5 degrees C and a critical micelle concentration (CMC) of 12.6 mg L(-1). Transmission electron microscopy (TEM) shows that the micelles exhibit a nanospheric morphology within a narrow size range of approximately 10-30 nm. A study of controlled release reveals that the self-assembled micelles have great potential as drug carriers.

3T3 Cells↗
PubMed1998

Pulmonary epithelial permeability and gas exchange: a comparison of inverse ratio ventilation and conventional mechanical ventilation in oleic acid-induced lung injury in rabbits.

STUDY OBJECTIVE: (1) To explore the interaction between mechanical ventilation and oleic acid (OA)-induced lung injury on indexes of pulmonary gas exchange and epithelial permeability, and (2) to compare this interaction using two different modes of ventilation: pressure-controlled inverse ratio ventilation (PCIRV) and volume-controlled ventilation with positive end-expiratory pressure (VCV PEEP). DESIGN: Randomized animal study. SETTING: Experimental laboratory investigation at Södersjukhuset, Stockholm, Sweden. ANIMALS: Twenty-four New Zealand white rabbits. INTERVENTIONS: (1) Ventilation with PCIRV (n=6) or VCV PEEP (n=6) for 6 h at equal end-expiratory alveolar pressure levels of 5 cm H2O followed by induction of lung injury (IV injection of OA 0.15 mL/kg). (2) Induction of lung injury followed by 6 h of ventilation with either PCIRV (n=6) or VCV PEEP (n=6) as described above. MEASUREMENTS AND RESULTS: Lung mechanics, heart rate, BP, and gas exchange results were equal at baseline. In group A, after 1 h of ventilation, mean airway pressure was 11.9+/-4.4 with PCIRV and 8.3+/-1.0 cm H2O with VCV PEEP (p<0.05). Forty minutes after OA injection, PaO2/fraction of inspired oxygen (FIO2) was 24+/-10 kPa with PCIRV and 44+/-15 kPa with VCV PEEP (p<0.05). Mean airway pressure was higher and peak airway pressure was lower with PCIRV. In group B, after 6 h of ventilation, PaO2/FIO2 was 17+/-5 kPa with PCIRV and 43+/-8 kPa with VCV PEEP (p<0.01). Systemic BP was lower with PCIRV and mean airway pressure was higher. Technetium-99m diethylene triamine penta-acetic acid lung clearance: In group A, curves were monoexponential with both PCIRV (half-life time [T 1/2], 21+/-8 min and VCV PEEP (T 1/2, 126+/-59 min, p<0.005) until injection of OA. In the VCV PEEP-treated animals, a marked increase in clearance rate was observed within 60 s of OA injection (T 1/2, 13+/-9 min, p<0.001). Fifteen minutes after OA injections, T 1/2 had decreased to 38+/-17 min with VCV PEEP. In the animals treated with PCIRV, OA injection did not lead to a significant change in clearance rate, although the elimination pattern was observed to change from single-compartment to multicompartment type. In group B, clearance curves were monoexponential with both ventilatory modes. There was no significant difference in clearance rate between PCIRV (T 1/2, 25+/-9 min) and VCV PEEP (T 1/2, 36+/-16 min, not significant). CONCLUSIONS: The observation that PaO2 was lower in the PCIRV-treated groups must be interpreted with caution in this animal study with relatively few observations. The finding may reflect differences in the effect of OA injection in the two ventilatory modes. It is also possible that externally applied PEEP is more effective than PCIRV in increasing oxygen tension, either because of a less inhomogenous distribution of ventilation and perfusion or for other reasons. The clearance results imply that PCIRV causes an alteration in lung epithelial or membrane function in comparison to VCV PEEP. This functional difference is most likely caused by the large time-weighted lung volume produced by pressure control in combination with a prolonged inspiration. Induction of high permeability lung injury with OA eliminates the difference between PCIRV and VCV PEEP. It remains to be established whether these findings are relevant with regard to ventilator-associated structural lung injury in man.

Acute Disease↗
PubMed2002

Conversion of fatty acids by Bacillus sphaericus-like organisms.

Bacillus sphaericus species are mesophilic round-spored organisms that readily utilize fatty acid-based surfactants during growth, but their ability to modify fatty acids is unknown. Among 57 B. sphaericus-like strains tested for fatty acid transformation activity in Wallen fermentation (WF) medium, ten converted oleic acid to a new product determined by gas chromatography - mass spectrometry (GC-MS) to be 10-ketostearic acid (10-KSA). Additionally, a few other strains converted ricinoleic acid and linoleic acid to new products that remain to be characterized. Unlike most microbial hydrations of oleic acid, which produce a mixture of 10-KSA and 10-hydroxystearic acid, the conversion of oleic acid by B. sphaericus strains was unique in that 10-KSA was the sole reaction product. By replacing dextrose with sodium pyruvate in WF and adjusting to pH 6.5, conversion of oleic acid to 10-KSA by strain NRRL NRS-732 was improved from about 11% to more than 60%. Using the defined optimal conditions, the conversion reaction was scaled up in a stirred-batch reactor by using technical-grade oleic acid as substrate. This is the first report on the characterization of fatty acid conversions by B. sphaericus species.

Bacillus↗
PubMed2006

Characterization of a hemocyte intracellular fatty acid-binding protein from crayfish (Pacifastacus leniusculus) and shrimp (Penaeus monodon).

Intracellular fatty acid-binding proteins (FABPs) are small members of the superfamily of lipid-binding proteins, which occur in invertebrates and vertebrates. Included in this superfamily are the cellular retinoic acid-binding proteins and retinol-binding proteins, which seem to be restricted to vertebrates. Here, we report the cDNA cloning and characterization of two FABPs from hemocytes of the freshwater crayfish Pacifastacus leniusculus and the shrimp Penaeus monodon. In both these proteins, the binding triad residues involved in interaction with ligand carboxylate groups are present. From the sequence and homology modeling, the proteins are probably FABPs and not retinoic acid-binding proteins. The crayfish transcript (plFABP) was detected at high level in hemocytes, hepatopancreas, intestine and ovary and at low level in hematopoietic tissue and testis. Its expression in hematopoietic cells varied depending on the state of the crayfish from which it was isolated. Expression was 10-15 times higher in cultures isolated from crayfish with red colored plasma, in which hemocyte synthesis was high, if retinoic acid was added to the culture medium. In normal colored crayfish, with normal levels of hemocytes, no increase in expression of p1FABP was detected. Two other putative plFABP ligands, stearic acid and oleic acid, did not have any effect on plFABP expression in hematopoietic cells. These results suggest that retinoic acid-dependent signaling may be present in crustaceans.

Amino Acid Sequence↗
PubMed1975

Fatty acid composition of some cellular membranes of fetal rat liver.

The fatty acid composition of lipids of inner mitochondrial membrane, rough and smooth endoplasmic reticulum of adult and fetal rat liver has been determined. Subcellular membranes of fetal liver show a higher content of palmitic acid and oleic acid and a lower content of stearic acid and arachidonic acid as compared to subcellular membranes of the adult liver. The activity of citrate lyase and acetyl-CoA carboxylase of rat liver cytosol has been determined as a function of age. It is concluded that the differences are due to a relative deficiency of the fatty acid elongation system. The higher degree of saturation of the fatty acids of the phospholipids of the fetal membranes may be the cause of altered permeability properties of these membranes, as illustrated by the slower rate of isoosmotic swelling in the presence of the ammonium salt of some of the Krebs cycle intermediates in fetal rat liver mitochondria.

ATP Citrate (pro-S)-Lyase↗
PubMed2006

Protective effect of Mediterranean fish oil extracts on heat-induced denaturation of albumin.

Three oily extracts, obtained by acetone extraction from the entrails of different varieties of Mediterranean fishes, such as mackerel (Scomber scombrus), sardine (Sardina pilchardus) and horse mackerel (Trachurus mediterraneus), were characterized to determine their unsaturated fatty acid content. In an in-vitro model, their inhibitory effect was then evaluated against protein aggregation and their protective efficacy against heat-induced albumin denaturation assessed. The fish oil extracts tested in this study presented a significant amount of unsaturated fatty acids; in particular the extract obtained from the entrails of horse mackerel proved to have higher concentrations of DHA (docosahexaenoic acid) and oleic acid compared with the other two oils. The in-vitro study revealed an interesting protective effect of the oil extracts (particularly the horse mackerel extract) against heat-induced denaturation of albumin.

Animals↗
PubMed1984

Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise.

Nine insulin-dependent diabetics and six healthy controls were studied at rest, during, and after 60 min of bicycle exercise at a work load corresponding to 45% of their maximal oxygen intake. The catheter technique was employed to determine splanchnic and leg exchange of metabolites. FFA turnover and regional exchange was evaluated using [14C]oleate infusion. Basal glucose (13.8 +/- 1.1 mmol/l), ketone body (1.12 +/- 0.12 mmol/l), and FFA (967 +/- 110 mumol/l) concentrations were elevated in the diabetics in comparison with controls. In the resting state, splanchnic ketone acid production in the diabetics was 6-10-fold greater than in controls. Uptake of oleic acid by the splanchnic bed was increased 2-3-fold, and the proportion of splanchnic FFA uptake converted to ketones (61%) was threefold greater than in controls. In contrast, splanchnic fractional extraction of oleic acid was identical in diabetics and controls. A direct relationship was observed between splanchnic uptake and splanchnic inflow (plasma concentration X hepatic plasma flow) of oleic acid that could be described by the same regression line in the diabetic and control groups. During exercise, splanchnic ketone production rose in both groups. In the control group the increase in ketogenesis was associated with a rise in splanchnic inflow and in uptake of oleic acid, a rise in splanchnic fractional extraction of oleate, and an increase in the proportion of splanchnic FFA uptake converted to ketone acids from 20-40%. In the diabetic group, the increase in ketogenesis occurred in the absence of a rise in splanchnic inflow or uptake of oleic acid, but was associated with an increase in splanchnic fractional extraction of oleic acid and a marked increase in hepatic conversion of FFA to ketones, so that the entire uptake of FFA was accountable as ketone acid output. Splanchnic uptake of oleic acid correlated directly with splanchnic oleic acid inflow in both groups, but the slope of the regression line was steeper than in the resting state. Plasma glucagon levels were higher in the diabetic group at rest and during exercise, while plasma norepinephrine showed a twofold greater increment in response to exercise in the diabetic group (to 1,400-1,500 pg/ml). A net uptake of ketone acids by the leg was observed during exercise but could account for less than 5% of leg oxidative metabolism in the diabetics and less than 1% in controls. Despite the increase in ketogenesis during exercise, a rise in arterial ketone acid levels was not observed in the diabetics until postexercise recovery, during which sustained increments to values of 1.8-1.9 mmol/l and sustained increases in splanchnic ketone production were observed at 30-60 min. The largest increment in blood ketone acids and in splanchnic ketone production above values observed in controls thus occurred in the diabetics after 60 min of recovery from exercise. We concluded that: (a) In the resting state, increased ketogenesis in the diabetic is a consequence of augmented splanchnic inflow of FFA and increased intrahepatic conversion of FFA to ketones, but does not depend on augmented fractional extraction of circulating FFA by the splanchnic bed. (b) Exercise-induced increases in ketogenesis in normal subjects are due to augmented splanchnic inflow and fractional extraction of FFA as well as increased intrahepatic conversion of FFA to ketones. (c) When exercise and diabetes are combined, ketogenesis increases further despite the absence of a rise in splanchnic inflow of FFA. An increase in splanchnic fractional extraction of FFA and a marked increase intrahepatic conversion of FFA to ketones accounts for the exaggerated ketogenic response to exercise in the diabetic. (d) Elevated levels of plasma glucagon and/or norepinephrine may account for the increased hepatic ketogenic response to exercise in the diabetic. (e) Ketone utilization by muscle increases during exercise but constitutes a quantitatively minor oxidative fuel for muscle even in the diabetic. (f) The accelerated ketogenesis during exercise in the diabetic continues unabated during the recovery period, resulting in an exaggerated postexercise ketosis.

Adult↗