S Venkatesan

Publications (39)147.69 Total impact

• Article: Glucose production in the human placenta.

  J Leonce, N Brockton, S Robinson, S Venkatesan, P Bannister, V Raman, K Murphy, K Parker, D Pavitt, T G Teoh, L Regan, A Burchell, P Steer, D G Johnston
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  ABSTRACT: Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study.
  Placenta 05/2006; 27 Suppl A:S103-8. · 3.69 Impact Factor
• Article: Increased leucine turnover in women during the third trimester of uncomplicated pregnancy.

  M Jolly, J Bertie, R Gray, P Bannister, S Venkatesan, D Johnston, S Robinson
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  ABSTRACT: Plasma amino acid concentrations decrease in pregnancy despite increased requirements for both maternal and fetal protein accretion. There are few published data on changes in amino acid turnover in pregnancy. The aim of this study is to test the hypotheses that (1) whole body nonoxidative leucine disposal (NOLD) is higher and (2) whole body oxidative leucine disposal (OLD) is lower in the third trimester of pregnancy than in the nonpregnant state. After an overnight fast 8 pregnant women between 33 and 35 weeks gestation had a primed infusion of labeled [1-(13)C] leucine and a prime dose of NaH(13)CO(3). Carbon dioxide production was measured using indirect calorimetry. Gas chromatography-mass spectrometry was used to determine (13)CO(2) enrichment of expired air and oxidative and nonoxidative leucine turnover by measuring (13)C keto-isocaproate plasma enrichment, which reflects intracellular leucine enrichment. Women acted as their own controls after the puerperium. Whole body leucine turnover expressed per unit body weight was increased in pregnancy (median [interquartile range or IQR]: pregnant = 103.1 [14.9] v nonpregnant = 90.1 [10.9] micromol/kg/h). The mean (+/-SD) of the differences was 11.4 +/- 5.6 micromol/kg/h, P =.0006. NOLD was increased in pregnancy (pregnant = 86.8 [10.1] v nonpregnant = 73.3 [9.5] micromol/kg/h). The mean (+/-SD) of the differences was 10.6 +/- 5.4 micromol/kg/h, P =.0008. OLD was not significantly altered in pregnancy (pregnant = 17.3 [4.5] v nonpregnant = 15.91 [2.4] micromol/kg/h). The mean (+/-SD) of the differences was 0.84 +/- 1.94 micromol/kg/h, P =.26. In conclusion, women have significantly higher NOLD in the third trimester of pregnancy than when not pregnant but there are no significant changes in OLD.
  Metabolism 06/2004; 53(5):545-9. · 2.66 Impact Factor
• Article: Metabolic effects of Troglitazone in patients with diet-controlled type 2 diabetes.

  A C J Robinson, J A R Jeffs, R G Gray, P A Bannister, H Mather, J J Gallagher, S Robinson, M Nattrass, S Venkatesan, D Halliday, D G Johnston
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  ABSTRACT: In order to study the mechanisms of action of Troglitazone (TGZ) in vivo in Type 2 diabetes, its effects were studied on glucose metabolism, lipolysis and very low-density lipoprotein (VLDL) apolipoprotein B100 (apoB) kinetics. A placebo-controlled, double-blind study was performed in 24 diet-treated patients randomized to receive TGZ 600 mg day(-1), TGZ 200 mg day(-1) or placebo for 8 weeks. Glucose and glycerol turnover were assessed after an overnight fast, and during sequential low-dose insulin infusions (0.01 U kg(-1) h(-1) followed by 0.015 U kg(-1) h(-1)) using 6,6-2H Glucose and 1,2,3-2H Glycerol. Very low-density lipoprotein apoB secretion was measured using l-13C-leucine, monitoring isotopic enrichment by gas chromatography-mass spectrometry. Treatment effects were analyzed by analysis of covariance, adjusting for baseline. Therapy resulted in a significant group differences in fasting plasma glucose adjusting for baseline (P=0.039). This was most evident at TGZ 600 mg daily [glucose decrease from (mean +/- SD) 9.2 +/- 2.7 to 6.6 +/- 0.9 mmol L(-1)]. HbA1c and insulin levels did not change significantly. Plasma nonesterified fatty acid (NEFA) levels decreased (P=0.045), most evidently at TGZ 200 mg daily, but glycerol was not significantly affected. Although no significant effects were observed on VLDL apoB or triglyceride concentrations, there were treatment differences in the absolute secretion rate of VLDL apoB of borderline (P=0.056) statistical significance, with a decrease observed at TGZ 600 mg daily [geometric mean, SD range, 0.94 (0.41-2.15) to 0.40 (0.14-1.13 mg kg(-1) h(-1))]. Very low-density lipoprotein apoB fractional secretion rate and pool size were unaffected. The VLDL triglyceride: apoB molar ratio differed between treatment groups (P=0.013), being higher in the TGZ 600 mg group [5714 (4128-7741) to 8092 (5669-11552)]. Neither glucose nor glycerol rates of appearance were significantly altered by TGZ and nor did TGZ affect their suppression by insulin. The PPARgamma agonist, troglitazone, decreases fasting glucose and NEFA levels in diet-treated Type 2 diabetes. It may also decrease VLDL particle secretion. These effects would be considered beneficial. The biological importance of the increase in VLDL-triglyceride enrichment warrants further study.
  European Journal of Clinical Investigation 02/2004; 34(1):29-36. · 3.02 Impact Factor
• Source

  Available from: endojournals.org

  Article: Hypopituitarsim is associated with triglyceride enrichment of very low-density lipoprotein.

  T Kearney, C Navas de Gallegos, A Chrisoulidou, R Gray, P Bannister, S Venkatesan, D G Johnston
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  ABSTRACT: The dyslipidemia associated with hypopituitarism may contribute to increased vascular mortality. The atherogenic potential of lipoproteins is determined not only by concentration but also by their composition. We therefore studied very low-density lipoprotein composition and apolipoprotein B kinetics in 16 hypopituitary subjects and 16 controls. Hypopituitarism was associated with reduced high-density lipoprotein cholesterol (0.98[0.82-1.18] vs. 1.35[1.15-1.41] mmol/liter, P < 0.001) and increased triglyceride concentrations (1.64[1.09-2.77] vs. 1.12[0.66-1.67] mmol/liter, P = 0.01). Total (P = 0.76) and low-density lipoprotein cholesterol (P = 0.56) concentrations were similar. Very low-density lipoprotein- triglyceride was significantly increased (1.48[1.02-2.55] vs. 0.9[0.31-2.30] mmol/liter, P = 0.004), but very low-density lipoprotein cholesterol levels were similar (P = 0.93). The molar ratios of very low-density lipoprotein-triglyceride:apolipoprotein B (6193[4283-9566] vs. 3599[3188-6854], P = 0.005) and very low-density lipoprotein-triglyceride:cholesterol (2.8[1.98-3.78] vs. 1.6[1.44-2.80], P < 0.003) were significantly increased; very low-density lipoprotein-cholesterol:apolipoprotein B molar ratios (P = 0.93) were similar. Very low-density lipoprotein apolipoprotein B fractional synthetic rate (a measure of apolipoprotein B catabolism, P = 0.42) and pool size (P = 0.63) were similar. The very low-density lipoprotein apolipoprotein B absolute synthetic rate (a measure of apolipoprotein B synthesis) tended to be higher in hypopituitarism (17.7[2.91-19.50] vs. 26.6[19.64-28.05] mg/kg per day, P = 0.24) but failed to reach statistical significance. The absolute synthetic rate, and hence very low-density lipoprotein production, correlated with very low-density lipoprotein triglyceride:apolipoprotein B ratio (P = 0.02, Rs = 0.63), suggesting that triglyceride enrichment of very low-density lipoprotein is important in the mechanism underlying very low-density lipoprotein overproduction in hypopituitarism. Because triglyceride-enriched lipoproteins are proatherogenic, this may contribute to the vascular mortality observed in hypopituitarism. The reasons for these observations are unknown; GH deficiency or routine endocrine replacement may be important.
  Journal of Clinical Endocrinology &amp Metabolism 08/2001; 86(8):3900-6. · 6.50 Impact Factor
• Article: Effects of growth hormone treatment on very-low density lipoprotein apolipoprotein B100 turnover in adult hypopituitarism.

  A Chrisoulidou, E Kousta, S Venkatesan, R Gray, P A Bannister, J J Gallagher, N Lawrence, D G Johnston
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  ABSTRACT: Adult hypopituitarism is associated with hyperlipidemia, mainly due to an increase of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) levels. Recent studies have shown that such patients exhibit increased hepatic secretion of VLDL apolipoprotein B100 (VLDL apo B100). To examine the effects of growth hormone (GH) replacement on VLDL apo B100 turnover, 13 GH-deficient hypopituitary patients (8 women and 5 men; aged 47 +/- 3 years, mean +/- SEM; body mass index [BMI], 30 +/- 2 kg/m2) entered a double-blind placebo-controlled study for 6 months (GH 0.125 IU/kg/wk for 4 weeks, and then 0.25 IU/kg/wk). GH was subsequently used in all patients for a further 6 months. A 6-hour [1-13C] leucine infusion was administered at baseline and at 6 months. The secretion rate of VLDL apo B100 was derived by kinetic analysis following quantitation of isotopic enrichment by gas chromatography/mass spectrometry. The GH-treated group (6 patients) demonstrated a similar fractional secretion rate (FSR) for VLDL apo B100 at 0 and 6 months. The pool size and absolute secretion rate (ASR) also were unaffected significantly by GH therapy. No significant changes were observed in the placebo group (7 patients). Treatment with GH for 6 months caused an increase in the high-density lipoprotein (HDL) cholesterol concentration (13 patients, 1.27 +/- 0.13 v 1.16 +/- 0.10 mmol/L, respectively, P = .05), whereas total cholesterol and triglyceride concentrations did not change. Nonesterified fatty acids (NEFAs) increased during GH therapy (471 +/- 43 micromol/L at 6 months v 349 +/- 49 micromol/L at baseline, P < .0005). The data suggest that GH does not affect VLDL apo B100 turnover in a significant way.
  Metabolism 05/2000; 49(5):563-6. · 2.66 Impact Factor
• Article: Glucose production by the human placenta in vivo.

  C H Prendergast, K H Parker, R Gray, S Venkatesan, P Bannister, J Castro-Soares, K W Murphy, R W Beard, L Regan, S Robinson, P Steer, D Halliday, D G Johnston
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  ABSTRACT: The human placenta transports glucose by facilitated diffusion down a concentration gradient from mother to fetus. It has previously been considered incapable of glucose synthesis. However, recent work has demonstrated the presence in placental tissue of glucose-6-phosphatase, which is required for the final step in the synthesis of glucose. Following continuous intravenous infusion into the maternal circulation of the stable isotope, 6,6-(2)H(2)glucose, during elective caesarean section, we have observed isotope dilution in the umbilical vein, without further dilution in the umbilical artery. Using a mathematical model containing maternal, placental and fetal compartments, the data were compatible with the release of glucose by the placenta. We conclude that the human placenta at term can produce glucose.
  Placenta 10/1999; 20(7):591-8. · 3.69 Impact Factor
• Article: Effects of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males.

  P Bordin, O A Bodamer, S Venkatesan, R M Gray, P A Bannister, D Halliday
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  ABSTRACT: To evaluate the effects of four weeks of fish oil supplementation on apolipoprotein B100 production and lipoprotein metabolism in normolipidaemic males. Very low density lipoprotein (VLDL) apolipoprotein B100 (apoB100) kinetics in ten healthy, white males, aged 22-43 y (mean 32 y) were investigated using 13C-leucine technique and gas chromatography-mass spectrometry before and after fish oil supplementation. All subjects received 10 g (1.8 g EPA, 1.2 g DHA)/d of fish oil concentrate for four weeks. Fish oil supplementation resulted in a decrease of total plasma VLDL (mean +/- s.d. 1.11 +/- 0.41 vs 0.87 +/- 0.28 mmol/l, P < 0.05) and triacylglycerol concentrations (0.74 +/- 0.27) vs 0.48 +/- 0.21 mmol/l, P < 0.01). VLDL apoB100 pool size was decreased without alteration of the fractional synthetic rate but a significant decrease of apoB100 production (2.23 +/- 0.90 vs 1.54 +/- 0.52 mg/dl/h, P < 0.02). Following fish oil supplementation plasma concentrations of glucose and insulin as well as lipoprotein and hepatic lipase activities were unchanged. Fasting plasma concentrations of non-esterified fatty acid (NEFA) were decreased (0.45 +/- 0.12 vs 0.33 +/- 0.10 mmol/l, P < 0.05). Dietary supplementation with fish oil in healthy males results in decreased VLDL-triacylglycerol concentrations through a decrease in VLDL particle synthesis. The decrease in NEFA substrate supply also contributes.
  European Journal of Clinical Nutrition 02/1998; 52(2):104-9. · 2.46 Impact Factor
• Article: Changes in fatty acid profile in plasma and very low density lipoprotein lipids after fish oil supplementation.

  C Ding, P Bordin, R M Gray, P A Bannister, D G Johnston, S Venkatesan
  Biochemical Society Transactions 12/1997; 25(4):S687. · 3.71 Impact Factor
• Article: Turnover of pro- and mature apolipoprotein A-I in diabetic patients and normolipidaemic controls.

  J J Gallager, R M Gray, P A Bannister, A Chrisoulidou, A C Robinson, D G Johnston, S Venkatesan
  Biochemical Society Transactions 12/1997; 25(4):S686. · 3.71 Impact Factor
• Article: Lipoproteins in non-insulin dependent diabetes mellitus (NIDDM).

  C G Hobbs, M Kodikara, R Gray, P Bordin, A Robinson, P J Pacy, S Venkatesan, D Halliday
  Biochemical Society Transactions 06/1996; 24(2):153S. · 3.71 Impact Factor
• Article: Apo C subclasses from non-insulin-dependent diabetic patients--a quantitative comparison with control subjects.

  S Venkatesan, H Imrie, S Read, D Halliday
  Biochemical Society Transactions 06/1995; 23(2):278S. · 3.71 Impact Factor
• Article: Very low density lipoprotein sub-classes: separation and characterization from normo and hyper-lipidaemic subjects.

  S Venkatesan, H Imrie, P Smethurst, D Halliday
  Biochemical Society Transactions 06/1994; 22(2):101S. · 3.71 Impact Factor
• Article: Comparison of apo C subclasses from normal and hypertriglyceridaemic subjects after 4 days on high (80%) and moderate (50%) carbohydrate diet.

  S Venkatesan, H Imrie, S Read, D Halliday
  Biochemical Society Transactions 06/1994; 22(2):102S. · 3.71 Impact Factor
• Article: Metabolism of apolipoprotein B-100 and of triglyceride-rich lipoprotein particles in the absence of functional lipoprotein lipase.

  P J Pacy, K A Mitropoulos, S Venkatesan, G F Watts, B E Reeves, D Halliday
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  ABSTRACT: Cholesterol and triglyceride in the various lipoprotein fractions were determined in five patients without functional lipoprotein lipase (LPL) while on their habitual therapeutic diet of 'low fat' content (20-25 g/day). They were also studied following 3 days on either a 'minimal fat' diet (< 15 g/day) or a 'moderate fat' diet (45-50 g/day). Values obtained were compared with the respective levels measured in five control subjects on a 'normal fat' (70-90 g/day) diet. The patients had hypertriglyceridaemia (type V hyperlipoproteinaemia) under all dietary conditions. Cholesterol and triglyceride levels in plasma and in the chylomicron fraction increased in the patients with increasing dietary fat. In the very low density lipoprotein (VLDL) fraction from the patients, triglyceride levels also increased with the dietary fat intake, but cholesterol levels were similar under all dietary conditions. In the patients, cholesterol concentrations in the low (LDL) and high density (HDL) lipoprotein fractions were significantly lower than the respective levels in controls, but the ratio of cholesterol to triglyceride levels in both of these lipoprotein fractions decreased with the dietary fat intake. VLDL apolipoprotein B-100 (apo B-100) pool size was similar in the patients on the two test diets (P = 0.95) and 3.5-fold higher than in five healthy volunteers on a normal fat diet. Using a stable isotope enrichment method, the kinetics of apo B-100 were investigated in the patients under the last two dietary conditions. The fractional and absolute secretion rates of the apolipoprotein in the patients did not vary with fat intake, but fractional secretion rates were significantly lower and the absolute secretion rates were significantly higher in the patients than the respective values in the controls. These results are consistent with the hypothesis that in the absence of LPL activity the metabolism of chylomicron and VLDL particles in the circulation results in triglyceride-rich LDL and HDL particles that are taken up by the liver at increased rates, thus reducing the plasma LDL and HDL cholesterol concentrations, whereas the products of hydrolysis of these particles induce an increased rate of synthesis of triglyceride and an increased rate of secretion of VLDL apo B-100.
  Atherosclerosis 12/1993; 103(2):231-43. · 3.79 Impact Factor
• Article: Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia.

  S Venkatesan, P Cullen, P Pacy, D Halliday, J Scott
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  ABSTRACT: Familial combined hyperlipidemia (FCHL) may be genetically and metabolically more heterogeneous than previously thought. A consistent feature is an increase in circulating very-low-density lipoprotein (VLDL) apolipoprotein (apo) B, which could be due to either an increase in apoB production or a decrease in its catabolism. Therefore, we directly measured VLDL apoB production in the postabsorptive state in seven FCHL subjects (four male, three female) and seven normal control subjects (three male, four female) by using L-[1-13C]leucine as an endogenous label. Mean age and body mass index did not differ significantly between the two groups. The mean total cholesterol levels were 4.7 +/- 0.8 and 8.8 +/- 1.6 mmol/L (+/- SD, P < .01) and the mean triglyceride levels were 0.84 +/- 0.14 and 3.30 +/- 1.10 mmol/L (+/- SD, P < .01) in the control and FCHL groups, respectively. Although the fractional production rate of VLDL apoB was 38% lower in the FCHL group than in the control subjects (0.11 +/- 0.03 versus 0.18 +/- 0.02 pool/h; mean +/- SD, P < .01), its absolute production rate was 2.7 times greater (534 +/- 193 micrograms/kg per hour in FCHL versus 196 +/- 71 micrograms/kg per hour in control subjects; mean +/- SD, P < .01). There was a linear relation (r = 0.8, P = .03) between triglyceride levels and the VLDL apoB production rate in FCHL, the slope of which indicated a similar VLDL triglyceride-to-apoB ratio in the FCHL and control groups. We conclude that FCHL is a metabolically coherent disorder and that the increase in circulating apoB and triglyceride levels in FCHL is due to secretion of an increased number of VLDL particles, each containing, on average, a normal amount of triglyceride and one molecule of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)
  Arteriosclerosis and thrombosis: a journal of vascular biology / American Heart Association 07/1993; 13(7):1110-8.
• Source

  Available from: ajcn.org

  Article: Apolipoprotein metabolism: a stable-isotope approach.

  D Halliday, S Venkatesan, P Pacy
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  ABSTRACT: Lipids are the major fuel of the body. Efficient functioning as an energy source dictates that lipids must be transportable in the plasma from the point of synthesis and assembly to the storage depots and finally to the tissues to provide energy through oxidative metabolism. Complex lipid forms are transported through the plasma as lipoprotein particles. These particles, secreted from the intestine and liver, have nonpolar outer surface composed of cholesterol, phospholipids, and apolipoproteins. Apolipoproteins are essential for the production, secretion, and continued structural integrity of the various lipoprotein particles and thus play a pivotal role in the control mechanisms of lipid transport. Apolipoproteins regulate specific enzyme activities and modulate plasma lipoprotein clearance through receptor-mediated processes. Quantitative information regarding the rates of synthesis and catabolism of apolipoproteins is vital to an understanding of their metabolism in health and disease. General considerations are followed by a specific use of stable-isotope methodology to quantitative the rate of synthesis of very-low-density-lipoprotein apolipoprotein B-100 (VLDL apo B-100) in control and familial-combined-hyperlipidemic (FCHL) patients.
  American Journal of Clinical Nutrition 06/1993; 57(5 Suppl):726S-730S; discussion 730S-731S. · 6.67 Impact Factor
• Article: Assessment of particle size of very low density lipoproteins by morphometry.

  S Venkatesan, P Fryer, N Powell, A Herd, P J Pacy, D Halliday
  Biochemical Society Transactions 06/1993; 21(2):152S. · 3.71 Impact Factor
• Article: Very low density lipoprotein apo beta 100--comparison of several methods for protein assay.

  S Venkatesan, S Read, A Herd, P J Pacy, P A Bannister, D Halliday
  Biochemical Society Transactions 06/1993; 21(2):153S. · 3.71 Impact Factor
• Article: Direct measurement of apo B-100 production rate in fed and fasted normolipidaemic adult male volunteers.

  P J Pacy, S Venkatesan, A Collins, D Halliday
  Biochemical Society Transactions 06/1992; 20(2):101S. · 3.71 Impact Factor
• Article: Fractional and absolute synthetic rate of very low density lipoprotein apo B-100 in lipoprotein lipase deficient patients.

  S Venkatesan, P J Pacy, K A Mitropoulos, G F Watts, D Halliday
  Biochemical Society Transactions 06/1992; 20(2):103S. · 3.71 Impact Factor