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1.
Nutr Diabetes ; 3: e88, 2013 Sep 16.
Article in English | MEDLINE | ID: mdl-24042701

ABSTRACT

BACKGROUND: Obesity is associated with low-grade systemic inflammation, in part because of secretion of proinflammatory cytokines, resulting into peripheral insulin resistance (IR). Increased oxidative stress is proposed to link adiposity and chronic inflammation. The effects of endurance exercise in modulating these outcomes in insulin-resistant obese adults remain unclear. We investigated the effect of endurance exercise on markers of oxidative damage (4-hydroxy-2-nonenal (4-HNE), protein carbonyls (PCs)) and antioxidant enzymes (superoxide dismutase (SOD), catalase) in skeletal muscle; urinary markers of oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane); and plasma cytokines (C-reactive protein (CRP), interleukin-6 (IL-6), leptin, adiponectin). METHODS: Age- and fitness-matched sedentary obese and lean men (n=9 per group) underwent 3 months of moderate-intensity endurance cycling training with a vastus lateralis biopsy, 24-h urine sample and venous blood samples taken before and after the intervention. RESULTS: Obese subjects had increased levels of oxidative damage: 4-HNE (+37%; P0.03) and PC (+63%; P0.02); evidence of increased adaptive response to oxidative stress because of elevated levels of copper/zinc SOD (Cu/ZnSOD) protein content (+84%; P0.01); increased markers of inflammation: CRP (+737%; P0.0001) and IL-6 (+85%; P0.03), and these correlated with increased markers of obesity; and increased leptin (+262%; P0.0001) with lower adiponectin (-27%; P0.01) levels vs lean controls. Training reduced 4-HNE (-10%; P0.04), PC (-21%; P0.05), 8-isoprostane (-26%; P0.02) and leptin levels (-33%; P0.01); had a tendency to decrease IL-6 levels (-21%; P=0.07) and IR (-17%; P=0.10); and increased manganese SOD (MnSOD) levels (+47%; P0.01). CONCLUSION: Endurance exercise reduced skeletal muscle-specific and systemic oxidative damage while improving IR and cytokine profile associated with obesity, independent of weight loss. Hence, exercise is a useful therapeutic modality to reduce risk factors associated with the pathogenesis of IR in obesity.

2.
Metabolism ; 50(7): 767-70, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11436179

ABSTRACT

Glucosamine sulfate is a controversial osteoarthritis remedy that is presumed to stimulate articular cartilage glycosaminoglycan synthesis by increasing glucosamine concentrations in the joint space. However, this is not plausible because even large oral doses of the product have no effect on serum glucosamine concentrations. We propose instead that sulfate could mediate the clinical benefit attributed to this treatment. Sulfate is required for glycosaminoglycan synthesis, and unlike glucosamine, its serum level can be modified by dietary and other factors. In this study, we tested whether oral glucosamine sulfate increases serum sulfate concentrations and whether the sulfate concentration in the synovial fluid reflects that in the serum. The serum sulfate concentration of 7 normal subjects was 331 +/- 21 micromol/L before ingestion of 1.0 g glucosamine sulfate and 375 +/- 17 micromol/L 3 hours after (P <.05). Serum sulfate concentrations decreased from 325 +/- 19 to 290 +/- 19 micromol/L when the same dose of glucosamine sulfate was ingested with 1.0 g of the analgesic drug acetaminophen, which is largely metabolized by sulfation (P <.05). Unlike glucosamine sulfate, oral sodium sulfate did not significantly increase the serum sulfate concentration. Synovial fluid and serum sulfate concentrations were closely similar when measured in 15 patients undergoing diagnostic needle aspiration of a knee effusion (r =.99, slope =.97, P <.0001). These results do not prove that glucosamine sulfate improves osteoarthritis, but considered with other data, they do provide a plausible biochemical mechanism for its reported beneficial effects. This hypothesis is clinically relevant because it predicts that nonsulfate salts of glucosamine will be ineffective and that renal function, diet, and concurrent acetaminophen therapy could confound clinical trials of this therapy.


Subject(s)
Glucosamine/therapeutic use , Sulfates/metabolism , Acetaminophen/pharmacology , Adult , Analgesics, Non-Narcotic/pharmacology , Female , Glucosamine/administration & dosage , Glucosamine/antagonists & inhibitors , Humans , Male , Sulfates/blood , Synovial Fluid/metabolism
3.
Am J Physiol Endocrinol Metab ; 281(2): E341-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11440911

ABSTRACT

One feature of the adaptation to dietary protein restriction is reduced urea production over the hours after consumption of a test meal of fixed composition. This adaptation is impaired in conventionally treated insulin-dependent diabetes mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab 272: E59--E67, 1997). We have now tested the response to a test meal containing less protein and included as a main outcome variable the production of sulfate, a specific indicator of sulfur amino acid catabolism. Six normal men consumed a mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They followed the identical protocol twice. Six subjects with insulin-dependent diabetes consumed the test meal while adapted to their customary high-protein diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative postmeal urea N and S production by 22--29% and 49--52%, respectively (both P < 0.05). Similar results were obtained for a postmeal collection period of 6 h. The response of the diabetic subjects was normal. We conclude that reductions in postmeal urea and sulfate production after protein restriction are reproducible and are evident using a postmeal collection period as short as 6 h. Sulfate production effectively depicts fed-state adaptation to protein restriction.


Subject(s)
Diabetes Mellitus, Type 1/metabolism , Diet, Protein-Restricted , Dietary Proteins/metabolism , Postprandial Period , Sulfates/metabolism , Adult , Alanine/metabolism , Blood Glucose , Carbon Isotopes , Female , Humans , Male , Nitrogen Isotopes , Urea/blood , Urea/urine
4.
Am J Physiol Endocrinol Metab ; 281(2): E349-56, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11440912

ABSTRACT

Six normal men consumed a mixed test meal while adapted to high (1.5 g. kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They completed this protocol twice: when the test meals included 3 mg/kg of [(15)N]alanine ([(15)N]Ala) and when they included 30 mg/kg of intrinsically labeled [(15)N]Spirulina platensis ([(15)N]SPI). Six subjects with insulin-dependent diabetes mellitus (IDDM) receiving conventional insulin therapy consumed the test meal with added [(15)N]Ala while adapted to their customary high-protein diet. Protein restriction increased serum alanine, glycine, glutamine, and methionine concentrations and reduced those of leucine. Whether the previous diet was high or low in protein, there was a similar increase in serum alanine, methionine, and branched-chain amino acid concentrations after the test meal and a similar pattern of (15)N enrichment in serum amino acids for a given tracer. When [(15)N]Ala was included in the test meal, (15)N appeared rapidly in serum alanine and glutamine, to a minor degree in leucine and isoleucine, and not at all in other circulating amino acids. With [(15)N]SPI, there was a slow appearance of the label in all serum amino acids analyzed. Despite the different serum amino acid labeling, protein restriction reduced the postmeal transfer of dietary (15)N in [(15)N]Ala or [(15)N]SPI into [(15)N]urea by similar amounts (38 and 43%, respectively, not significant). The response of the subjects with IDDM was similar to that of the normal subjects. Information about adaptive reductions in dietary amino acid catabolism obtained by adding [(15)N]Ala to a test meal appears to be equivalent to that obtained using an intrinsically labeled protein tracer.


Subject(s)
Alanine/metabolism , Diabetes Mellitus, Type 1/metabolism , Diet, Protein-Restricted , Nitrogen Isotopes/metabolism , Urea/metabolism , Aspartic Acid/blood , Bacterial Proteins , Female , Gas Chromatography-Mass Spectrometry , Glutamine/blood , Glycine/blood , Humans , Isoleucine/blood , Leucine/blood , Male , Methionine/blood , Nitrogen Isotopes/analysis , Postprandial Period/physiology , Spirulina
5.
Am J Physiol Endocrinol Metab ; 280(6): E857-66, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11350767

ABSTRACT

There is no fully satisfactory method for measuring amino acid catabolism in the nonsteady state that follows normal protein consumption. Because sulfate is the major product of sulfur amino acid catabolism, we tested whether its production can be accurately depicted using simple tracer or nontracer approaches under basal conditions and after the intravenous administration of a known amount of sulfate. In the basal postabsorptive state, serum sulfate concentration and urinary sulfate excretion remained constant for many hours, but the apparent steady-state serum sulfate rate of appearance achieved with primed continuous oral administration of sodium [(34)S]sulfate was 20% higher than urinary sulfate excretion. By contrast, after magnesium sulfate infusion, the increase in sulfate production above basal accounted for 95% over 6 h and 98% over 9 h of the administered dose when measured simply as urinary inorganic sulfate excretion corrected for changes in its extracellular fluid content. Using the latter method, we measured sulfate production after oral methionine and intravenous infusion of methionine in a mixture of other essential amino acids. Sulfate production above basal accounted for 59% over 6 h and 75% over 9 h of the oral methionine dose. Similar results were obtained with the mixed amino acid infusion, but interpretation of the latter experiment was limited by the mild protein sparing (and, hence, reduced endogenous sulfate production) induced by the amino acid infusion. We conclude that a simple nontracer method can provide an accurate measure of sulfate production and, hence, sulfur amino acid catabolism over collection periods as short as 6 h after a test meal. A significant portion of the sulfur derived from methionine appears to be retained in nonprotein compounds immediately after its ingestion.


Subject(s)
Eating/physiology , Methionine/pharmacokinetics , Sulfates/blood , Administration, Oral , Adult , Amino Acids/administration & dosage , Amino Acids/pharmacokinetics , Fasting/physiology , Glutathione/metabolism , Humans , Male , Methionine/administration & dosage , Oxidation-Reduction , Reproducibility of Results , Sulfates/pharmacokinetics , Sulfur Isotopes/pharmacokinetics
6.
J Nutr ; 129(3): 722-7, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10082781

ABSTRACT

The volume of human extracellular water (ECW) may be estimated from the sulfate space (SS). Although it may better approximate ECW volume than the bromide space, a common alternative, SS measurement is limited by the need to administer a radioactive substance, sodium [35S]sulfate. In this paper, we demonstrate the measurement of the SS using the stable isotope, sodium [34S]sulfate. Eight healthy nonobese men ingested 0.50-0.78 mg (3.47-5.42 micromol) Na234SO4/kg body weight and 30 mg NaBr/kg body weight. Sulfate concentrations and 34SO4 enrichments were measured by electrospray tandem mass spectrometry before and during the 5 h after tracer administration. SS was calculated by linear extrapolation of the natural logarithm of serum 34SO4 concentrations obtained at h 2, 3 and 4 compared with h 3, 4 and 5. The SS obtained using values between h 3 and 5 (187 +/- 17 mL/kg) was similar to published determinations using intravenous or oral radiosulfate, and was 80% of the simultaneously measured corrected bromide space (234 +/- 10 mL/kg, P = 0.01). Oral sodium [34S]sulfate administration is a suitable technique for measuring ECW and avoids radiation exposure.


Subject(s)
Body Water , Extracellular Space , Sulfates , Adult , Bromides , Female , Humans , Male , Mass Spectrometry , Reference Values , Sodium Compounds , Sulfates/analysis , Sulfur Isotopes
7.
Metabolism ; 47(9): 1145-51, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9751246

ABSTRACT

We determined whether a customary diet high or low in protein (1) influences postabsorptive amino acid catabolism, nitrogen (N) balance, and hepatic glucose output (HGO) in normal subjects or patients with non-insulin-dependent diabetes mellitus (NIDDM) or (2) alters blood glucose levels in NIDDM. Eight normal young adults and five obese middle-aged persons with NIDDM consumed low-protein (0.8 g/kg lean body mass [LBM]) or high-protein (3.0 g/kg LBM) diets at maintenance energy for consecutive 7-day periods. Fasting and average blood glucose and N balance were measured daily. The level of dietary protein had no effect on the basal plasma leucine rate of appearance (Ra) or urinary 3-methylhistidine excretion in either subject group. Basal leucine oxidation (and by inference, whole-body amino acid catabolism) was reduced on the low-protein diet but basal HGO was not, and although exogenous glucose effectively suppressed HGO, it did not reduce leucine oxidation with either diet. After adaptation to the low-protein diet, N balance in both the normal and NIDDM subjects was close to zero. The low-protein diet reduced the fasting and daily blood glucose of the diabetic subjects by approximately 2 mmol/L (P < .05). We conclude that physiologic variation in dietary protein does not affect basal whole-body protein turnover or HGO in either normal young adults or obese middle-aged NIDDM subjects. However, protein restriction to the level of the average daily requirement significantly reduces postabsorptive and average daily blood glucose concentrations in persons with NIDDM.


Subject(s)
Diabetes Mellitus, Type 2/metabolism , Dietary Proteins/administration & dosage , Glucose/metabolism , Proteins/metabolism , Adult , Body Weight , Female , Humans , Liver/metabolism , Male
8.
Anal Biochem ; 261(1): 93-9, 1998 Jul 15.
Article in English | MEDLINE | ID: mdl-9683517

ABSTRACT

A reproducible and very sensitive method is described for the quantitation of inorganic sulfate in biological fluids by negative electrospray ionization tandem mass spectrometry. After addition to the sample of (34)S-labeled sodium sulfate internal standard and deproteinization with methanol, interfering bicarbonate anions are removed by acidification and chloride and phosphate by means of a single filtration step. The tandem mass spectrometer is used in neutral loss mode to detect HSO(4)(-) ions free of interference from residual isobaric H(2)PO(4)(-) ions. Organic sulfates do not interfere with the measurement. Serum and urinary inorganic sulfate concentrations measured with this technique agree closely with determinations by ion-exchange chromatography with conductivity detection. Unlike the latter method, this technique does not require dedicated equipment. The method is also suitable for measuring the ratio of (34)S-labeled sulfate to unlabeled sulfate in serum and hence represents an attractive alternative for the use of the radioactive (35)S isotope in human studies of body composition and oxidation of sulfur-containing substrates to sulfate.


Subject(s)
Spectrometry, Mass, Electrospray Ionization/methods , Sulfates/analysis , Chemistry Techniques, Analytical , Chromatography, Ion Exchange/methods , Humans , Sulfates/blood , Sulfates/urine
9.
Am J Physiol ; 274(3): E547-53, 1998 03.
Article in English | MEDLINE | ID: mdl-9530140

ABSTRACT

Urea production rate (Ra) is commonly measured using a primed continuous tracer urea infusion, but the accuracy of this method has not been clearly established in humans. We used intravenous infusions of unlabeled urea to assess the accuracy of this technique in normal, postabsorptive men under the following four different conditions: 1) tracer [13C]urea was infused under basal conditions for 12 h (control); 2) tracer [13C]urea was infused for 12 h, and unlabeled urea was infused from hours 4 to 12 at a rate twofold greater than the endogenous Ra ("step" infusion); 3) tracer [13C]urea was infused for 12 h, and unlabeled urea was infused from hours 4 to 8 ("pulse" infusion); and 4) tracer [13C]urea was infused for 9 h, and unlabeled alanine was infused at a rate of 120 mg.kg-1.h-1 (1.35 mmol.kg-1.h-1) from hours 4 to 9. Urea Ra was calculated using the isotopic steady-state equation (tracer infusion rate/tracer-to-tracee ratio), Steele's non-steady-state equation, and urinary urea excretion corrected for changes in total body urea. For each subject, endogenous urea Ra was measured at hour 4 of the basal condition, and the sum of this rate plus exogenous urea input was considered as "true urea input". Under control conditions, urea Ra at hour 4 was similar to that measured at hour 12. After 8-h step and 4-h pulse unlabeled urea infusions, Steele's non-steady-state equation underestimated true urea input by 22% (step) and 33% (pulse), whereas the nonisotopic method underestimated true urea input by 28% (step) and 10% (pulse). Similar conclusions were derived from the alanine infusion. These results indicate that, although Steele's non-steady-state equation and the nontracer method more accurately predict total urea Ra than the steady-state equation, they nevertheless seriously underestimate total urea Ra for as long as 8 h after a change in true urea Ra.


Subject(s)
Urea/metabolism , Adult , Alanine/administration & dosage , Alanine/metabolism , Carbon Isotopes , Humans , Male , Models, Biological , Postprandial Period , Radioactive Tracers , Radioisotope Dilution Technique , Reference Values , Time Factors , Urea/urine
10.
Am J Physiol ; 272(6 Pt 1): E1037-42, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9227449

ABSTRACT

We tested whether expansion of the plasma leucine pool distorts leucine or valine tracer kinetics, causing errors in the derived values of whole body proteolysis. Seven normal adults received a 10-h primed-continuous tracer infusion of L-[5,5,5-2H3]leucine, L-[(1-13)C]valine, and L-[(1-13)C]threonine, during the final 7 h of which L-leucine was infused at a rate that more than tripled the plasma leucine concentration. Leucine, valine, and threonine rates of appearance were converted to a common value of whole body proteolysis on the basis of their concentrations in body proteins. The conversion of labeled leucine and valine to their corresponding branched-chain alpha-keto and alpha-hydroxy acids was also monitored. Before the unlabeled leucine infusion, postabsorptive whole body proteolysis was estimated similarly by the three tracers (approximately 180 mg protein.kg-1.h-1. The leucine infusion reduced proteolysis by an average of 21% (P < 0.006), as estimated by use of valine or threonine kinetics, and by 10% by use of leucine kinetics (P < 0.02). No delay in the conversion of valine to alpha-ketoisovalerate occurred during the leucine infusion. Thus all three tracers indicated similar postabsorptive rates of whole body proteolysis and a reduction of proteolysis during leucine administration, although the magnitude of the effect was underestimated with use of the leucine tracer.


Subject(s)
Leucine/metabolism , Leucine/pharmacology , Threonine/metabolism , Valine/metabolism , Adult , Amino Acids/blood , Biotransformation , Carbon Isotopes , Deuterium , Female , Hemiterpenes , Humans , Keto Acids/blood , Kinetics , Male , Radioisotope Dilution Technique , Time Factors
11.
Am J Clin Nutr ; 61(1): 62-8, 1995 Jan.
Article in English | MEDLINE | ID: mdl-7825540

ABSTRACT

The objective was to determine the influence of consuming 50 g flaxseed/d for 4 wk on several indexes of nutrition in young healthy adults. During flaxseed consumption, alpha-linolenate was increased significantly in adipose tissue, and n-3 polyunsaturates were increased in plasma lipids. Plasma LDL cholesterol was also reduced by up to 8%, and total urinary lignan excretion was increased more than fivefold (P < 0.05). Muffins containing 25 g flaxseed did not differ significantly from control muffins in their content of thiobarbituric acid-reactive substances, and alpha-linolenate in the muffins was not significantly reduced by baking. Antioxidant vitamins and lipid hydroperoxides in plasma were not significantly affected by flaxseed consumption. Bowel movements per week increased by 30% while flaxseed was consumed (P < 0.05). We conclude that traditional flaxseed has modest beneficial effects on several indexes of nutritional status without compromising antioxidant status.


Subject(s)
Seeds , alpha-Linolenic Acid/metabolism , Adipose Tissue/metabolism , Adult , Anthropometry , Antioxidants/metabolism , Blood Glucose/drug effects , Cholesterol/blood , Cross-Over Studies , Defecation/drug effects , Dietary Fiber/administration & dosage , Fatty Acids, Omega-3/blood , Female , Humans , Lipid Peroxidation/drug effects , Male , Nutritional Status , alpha-Linolenic Acid/administration & dosage , alpha-Linolenic Acid/pharmacology
12.
Br J Nutr ; 69(2): 443-53, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8098222

ABSTRACT

Although high alpha-linolenic acid flaxseed (Linum usitatissimum) is one of the richest dietary sources of alpha-linolenic acid and is also a good source of soluble fibre mucilage, it is relatively unstudied in human nutrition. Healthy female volunteers consumed 50 g ground, raw flaxseed/d for 4 weeks which provided 12-13% of energy intake (24-25 g/100 g total fat). Flaxseed raised alpha-linolenic acid and long-chain n-3 fatty acids in both plasma and erythrocyte lipids, as well as raising urinary thiocyanate excretion 2.2-fold. Flaxseed also lowered serum total cholesterol by 9% and low-density-lipoprotein-cholesterol by 18%. Changes in plasma alpha-linolenic acid were equivalent when 12 g alpha-linolenic acid/d was provided as raw flaxseed flour (50 g/d) or flaxseed oil (20 g/d) suggesting high bioavailability of alpha-linolenic acid from ground flaxseed. Test meals containing 50 g carbohydrate from flaxseed or 25 g flaxseed mucilage each significantly decreased postprandial blood glucose responses by 27%. Malondialdehyde levels in muffins containing 15 g flaxseed oil or flour/kg were similar to those in wheat-flour muffins. Cyanogenic glycosides (linamarin, linustatin, neolinustatin) were highest in extracted flaxseed mucilage but were not detected in baked muffins containing 150 g flaxseed/kg. We conclude that up to 50 g high-alpha-linolenic acid flaxseed/d is palatable, safe and may be nutritionally beneficial in humans by raising n-3 fatty acids in plasma and erythrocytes and by decreasing postprandial glucose responses.


Subject(s)
Dietary Fiber/metabolism , Linolenic Acids/metabolism , Linseed Oil/metabolism , Nutritional Physiological Phenomena/physiology , Blood Glucose/metabolism , Cholesterol/blood , Cholesterol, LDL/blood , Erythrocytes/metabolism , Fatty Acids, Omega-3/metabolism , Female , Humans , Thiocyanates/urine , alpha-Linolenic Acid
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