Decrease in oxidative phosphorylation yield in presence of butyrate in perfused liver isolated from fed rats

<p>Abstract</p> <p>Background</p> <p>Butyrate is the main nutrient for the colonocytes but the effect of the fraction reaching the liver is not totally known. A decrease in tissue ATP content and increase in respiration was previously demonstrated when livers were perfused with short-chain fatty acids (SCFA) such as butyrate, or octanoate.</p> <p>In fed rats the oxidative phosphorylation yield was determined on the whole isolated liver perfused with butyrate in comparison with acetate and octoanoate (3 mmol/L). The rate of ATP synthesis was determined in the steady state by monitoring the rate of ATP loss after inhibition of (i) cytochrome oxidase (oxidative phosphorylation) with KCN (2.5 mmol/L) and (ii) glyceraldehyde 3-phosphate dehydrogenase (glycolysis) with IAA (0.5 mmol/L). The ATP flux, estimated by ³¹P Nuclear Magnetic Resonance, and the measured liver respiration allowed the ATP/O ratio to be determined.</p> <p>Results</p> <p>ATP turnover was significantly lower in the presence of butyrate (0.40 ± 0.10 μmoles/min.g, p = 0.001, n = 7) and octanoate (0.56 ± 0.10 μmoles/min.g, p = 0.01, n = 5) than in control (1.09 ± 0.13 μmoles/min.g, n = 7), whereas perfusion with acetate induced no significant decrease (0.76 ± 0.10 μmoles/min.g, n = 7). Mitochondrial oxygen consumption was unchanged in the presence of acetate (1.92 ± 0.16 <it>vs </it>1.86 ± 0.16 for control) and significantly increased in the presence of butyrate (p = 0.02) and octanoate (p = 0.0004) (2.54 ± 0.18 and 3.04 ± 0.15 μmoles/min.g, respectively). The oxidative phosphorylation yield (ATP/O ratio) calculated in the whole liver was significantly lower with butyrate (0.07 ± 0.02, p = 0.0006) and octanoate (0.09 ± 0.02, p = 0.005) than in control (0.30 ± 0.05), whereas there was no significant change with acetate (0.20 ± 0.02).</p> <p>Conclusion</p> <p>Butyrate or octanoate decrease rather than increase the rate of ATP synthesis, resulting in a decrease in the apparent ATP/O ratio. Butyrate as a nutrient has the same effect as longer chain FA. An effect on the hepatic metabolism should be taken into account when large quantities of SCFA are directly used or obtained during therapeutic or nutritional strategies.</p

Insulin induces a positive relationship between the rates of ATP and glycogen changes in isolated rat liver in presence of glucose; a (31)P and (13)C NMR study

BACKGROUND: There is an emerging theory suggesting that insulin, which is known to be the predominant postprandial anabolic hormone, is also a major regulator of mitochondrial oxidative phosphorylation in human skeletal muscle. However, little is known about its effects in the liver. Since there is a theoretical relationship between glycogen metabolism and energy status, a simultaneous and continuous investigation of hepatic ATP and glycogen content was performed in intact and isolated perfused liver by (31)P and (13)C nuclear magnetic resonance (NMR) The hepatic rates of ATP and glycogen changes were evaluated with different concentrations of insulin and glucose during continuous and short-term supply. RESULTS: Liver from rats fed ad libitum were perfused with Krebs-Henseleit Buffer (KHB)(controls) or KHB containing 6 mM glucose, 30 mM glucose, insulin alone, insulin + 6 mM glucose, insulin + 30 mM glucose. In the control, glycogenolysis occurred at a rate of -0.53 ± 0.021 %·min(-1) and ATP content decreased at a rate of -0.28 ± 0.029 %·min(-1). In the absence of insulin, there was a close proportional relationship between the glycogen flux and the glucose concentration, whereas ATP rates never varied. With insulin + glucose, both glycogen and ATP rates were strongly related to the glucose concentration; the magnitude of net glycogen flux was linearly correlated to the magnitude of net ATP flux: flux(glycogen )= 72.543(flux(ATP)) + 172.08, R(2 )= 0.98. CONCLUSION: Only the co-infusion of 30 mM glucose and insulin led to (i) a net glycogen synthesis, (ii) the maintenance of the hepatic ATP content, and a strong positive correlation between their net fluxes. This has never previously been reported. The specific effect of insulin on ATP change is likely related to a rapid stimulation of the hepatic mitochondrial oxidative phosphorylation. We propose that variations in the correlation between rates of ATP and glycogen changes could be a probe for insulin resistance due to the action of substrates, drugs or pathologic situations. Consequently, any work evaluating insulin resistance on isolated organs or in vivo should determine both ATP and glycogen fluxes

Improvement of leucocytic Na+K+ pump activity in uremic patients on low protein diet

Improvement of leucocytic Na+ K+ pump activity in uremic patients on low protein diet. Leucocytic Na+K+ pump activity was assessed in 20 patients with advanced renal failure. Na+K+-ATPase activity was reduced when compared with the values obtained from normal subjects (101.8 ± 48.6 versus 165.13 ± 8.9 µM of Pi hr-1 · g-1 P < 0.001) and the mean 86Rb uptake by U 937 cells was depressed by 38% after the addition of patients' sera. Subsequently, patients were put on a diet providing 0.3g protein/kg body weight daily and supplemented with ketoacids. After three months of dietary treatment Na+K+-ATPase activity increased to 142 ± 48.3 (P < 0.01) and reached normal values at the sixth month (162.8 ± 54.70 µM of Pi hr-1 · g-1; P < 0.001) whereas 86Rb uptake increased by 23 percent when compared to initial values. These data suggest that among the different mechanisms which have been advanced to explain the defects in the Na+ pump observed in uremic patients, circulating inhibitors deriving from alimentary protein intake may affect cation transport

Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial

<p>Abstract</p> <p>Background</p> <p>Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis.</p> <p>Methods</p> <p>The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups.</p> <p>Discussion</p> <p>The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15334496</p

Large kidneys predict poor renal outcome in subjects with diabetes and chronic kidney disease

<p>Abstract</p> <p>Background</p> <p>Renal hypertrophy occurs early in diabetic nephropathy, its later value is unknown. Do large kidneys still predict poor outcome in patients with diabetes and Chronic Kidney Disease (CKD)?</p> <p>Methods</p> <p>Seventy-five patients with diabetes and CKD according to a Glomerular Filtration Rate (GFR, by 51Cr-EDTA clearance) below 60 mL/min/1.73 m²or an Albumin Excretion Rate above 30 mg/24 H, had an ultrasound imaging of the kidneys and were cooperatively followed during five years by the Diabetology and Nephrology departments of the Centre Hospitalier Universitaire de Bordeaux.</p> <p>Results</p> <p>The patients were mainly men (44/75), aged 62 ± 13 yrs, with long-standing diabetes (duration:17 ± 9 yrs, 55/75 type 2), and CKD: initial GFR: 56.5 (8.5-209) mL/min/1.73 m², AER: 196 (20-2358) mg/24 H. Their mean kidney lenght (108 ± 13 mm, 67-147) was correlated to the GFR (r = 0.23, p < 0.05). During the follow-up, 9/11 of the patients who had to start dialysis came from the half with the largest kidneys (LogRank: p < 0.05), despite a 40% higher initial isotopic GFR. Serum creatinine were initially lower (Small kidneys: 125 (79-320) μmol/L, Large: 103 (50-371), p < 0.05), but significantly increased in the "large kidneys" group at the end of the follow-up (Small kidneys: 129 (69-283) μmol/L, Large: 140 (50-952), p < 0.005 vs initial). The difference persisted in the patients with severe renal failure (KDOQI stages 4,5).</p> <p>Conclusions</p> <p>Large kidneys still predict progression in advanced CKD complicating diabetes. In these patients, ultrasound imaging not only excludes obstructive renal disease, but also provides information on the progression of the renal disease.</p

Echelle visuelle analogique de faim (faisabilité, reproductibilité et applications)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les patients diabétiques de type 2 sont-ils plus sédentaires? (évaluation par actimétrie, comparaison à un groupe d hypertendus)

Les bénéfices de l'activité physique sur la santé sont démontrés. Les recommandations actuelles préconisent une activité physique quotidienne, elle fait partie de l'arsenal thérapeutique dans la prise en charge des patients diabétiques de type 2 (DT2). 87 sujets ont été recrutés auprès de médecins généralistes pour une évaluation de leur activité physique, 45 DT2 (20 femmes) et 42 hypertendus (20 femmes). Chaque sujet a porté durant 7 jours consécutifs un accéléromètre (Sensewear Armband), et répondu à deux questionnaires d'autoévaluation de l'activité physique ; le Ricci et l'IPAQ. Cette étude prospective, après comparaison DT2 versus HTA, n'a montré aucune différence significative pour la totalité des variables concernées, ainsi que pour celles issues des questionnaires. Après catégorisation en fonction du sexe, de l'âge, du BMI et l'accès à l'emploi, on observait sur l'ensemble de la population, à risque cardio-vasculaire, un niveau d'activité physique plus faible chez les femmes, chez les sujets de plus de 70 ans, en cas d'obésité et en l'absence d'activité professionnelle. Sur l'ensemble de l'échantillon (n = 87), les indices d'activité étaient inférieurs le Dimanche par rapport aux jours de semaine. Les patients diabétiques ont une activité physique semblable à une population d'hypertendus.BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Polyneuropathie diabétique et pressions plantaires (une évolution parallèle ?)

BORDEAUX2-BU Santé (330632101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF