Effects of exercise training and antioxidant R-ALA on glucose transport in insulin-sensitive rat skeletal muscle.

We have recently demonstrated (Saengsirisuwan V, Kinnick TR, Schmit MB, and Henriksen EJ, J Appl Physiol 91: 145-153, 2001) that exercise training (ET) and the antioxidant R-(+)-alpha-lipoic acid (R-ALA) interact in an additive fashion to improve insulin action in insulin-resistant obese Zucker (fa/fa) rats. The purpose of the present study was to assess the interactions of ET and R-ALA on insulin action and oxidative stress in a model of normal insulin sensitivity, the lean Zucker (fa/-) rat. For 6 wk, animals either remained sedentary, received R-ALA (30 mg. kg body wt(-1). day(-1)), performed ET (treadmill running), or underwent both R-ALA treatment and ET. ET alone or in combination with R-ALA significantly increased (P < 0.05) peak oxygen consumption (28-31%) and maximum run time (52-63%). During an oral glucose tolerance test, ET alone or in combination with R-ALA resulted in a significant lowering of the glucose response (17-36%) at 15 min relative to R-ALA alone and of the insulin response (19-36%) at 15 min compared with sedentary controls. Insulin-mediated glucose transport activity was increased by ET alone in isolated epitrochlearis (30%) and soleus (50%) muscles, and this was associated with increased GLUT-4 protein levels. Insulin action was not improved by R-ALA alone, and ET-associated improvements in these variables were not further enhanced with combined ET and R-ALA. Although ET and R-ALA caused reductions in soleus protein carbonyls (an index of oxidative stress), these alterations were not significantly correlated with insulin-mediated soleus glucose transport. These results indicate that the beneficial interactive effects of ET and R-ALA on skeletal muscle insulin action observed previously in insulin-resistant obese Zucker rats are not apparent in insulin-sensitive lean Zucker rats.     

Modulation of insulin resistance and hypertension by voluntary exercise training in the TG(mREN2)27 rat.

Hypertension is often accompanied by insulin resistance of skeletal muscle glucose transport. The male heterozygous TG(mREN2)27 rat, which harbors a mouse transgene for renin, displays local elevations in the renin-angiotensin system and exhibits markedly elevated systolic blood pressure (SBP). The present study was undertaken to characterize insulin-stimulated skeletal muscle glucose transport in male heterozygous TG(mREN2)27 rats and to evaluate the effect of voluntary exercise training on SBP and skeletal muscle glucose transport. Compared with normotensive Sprague-Dawley rats, TG(mREN2)27 rats displayed a 53% elevation (P < 0.05) in SBP, a twofold increase in plasma free fatty acid levels, and an exaggerated insulin response during an oral glucose tolerance test. Moreover, insulin-mediated glucose transport (2-deoxyglucose uptake) in isolated epitrochlearis and soleus muscles of TG(mREN2)27 animals was 33 and 43% less, respectively, than in Sprague-Dawley controls. TG(mREN2)27 rats ran voluntarily for 6 wk and achieved daily running distances of 6-7 km over the final 3 wk. Training caused a 36% increase in peak aerobic capacity and a 16% reduction in resting SBP. Fasting plasma insulin (21%) and free fatty acid (34%) levels were reduced in the trained TG(mREN2)27 rats. Whole body glucose tolerance was improved in the trained TG(mREN2)27 rats and was associated with increases of 39 and 50% in insulin-mediated glucose transport in epitrochlearis and soleus muscles, respectively. Whole muscle GLUT-4 protein was increased in the soleus (23%), but not in the epitrochlearis, of trained TG(mREN2)27 rats. These data indicate that the male heterozygous TG(mREN2)27 rat is a model of both hypertension and insulin resistance. Importantly, both of these defects can be beneficially modified by voluntary exercise training.     

Modelling the fission yeast cell cycle.

The molecular networks regulating basic physiological processes in a cell can be converted into mathematical equations (eg differential equations) and solved by a computer. The division cycle of eukaryotic cells is an important example of such a control system, and fission yeast is an excellent test organism for the computational modelling approach. The mathematical model is tested by simulating wild-type cells and many known cell cycle mutants. This paper describes an example where this approach is useful in understanding multiple rounds of DNA synthesis (endoreplication) in fission yeast cells that lack the main (B-type) mitotic cyclin, Cdc13. It is proposed that the key physiological variable driving progression through the cell cycle during balanced growth and division is the mass/DNA ratio, rather than the mass/nucleus ratio.     

Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827]

Background  

Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome.     

The genus Pyrus L. (Rosaceae) in south-west Europe and North Afkica

A multivariate morphometric study of the genus Pyrus in south-west Europe and North Africa shows that five species may be recognized in the area: P. bourgaeana Decne., P. communis L., P. cordata Dew., P. spinosa Forssk, and P. nivalis Jacq. Some valuable characters for identification of these species are proposed. In particular the width of fruit peduncle, petal size, leaf width and petiole length served to discriminate the taxa. Several names such as P. gharbiona Trab., P. cossonii Rehder (|M= P. longipes Balansa ex Coss. & Durieu) and P. boisseriana Buhse, are regarded as synonyms of P. cordata , while P. marnormis Trab. of P. bourgaeana. Consequently a check-list and a key to these species are provided.     

Effects of mutations in genes for proteins involved in disulphide bond formation in the periplasm on the activities of anaerobically induced electron transfer chains in Escherichia coli K12

The assembly of anaerobically induced electron transfer chains in Escherichia coli strains defective in periplasmic disulphide bond formation was investigated. Strains deficient in DsbA, DsbB or DipZ (DsbD) were unable to catalyse formate-dependent nitrite reduction (Nrf activity) or synthesize any of the known c-type cytochromes. The Nrf⁺ activity and cytochrome c content of mutants defective in DsbC, DsbE or DsbF were similar to those of the parental, wild-type strain. Neither DsbC expressed from a multicopy plasmid nor a second mutation in dipZ (dsbD) was able to compensate for a dsbA mutation by restoring nitrite reductase activity and cytochrome c synthesis. In contrast, only the dsbB and dipZ (dsbD) strains were defective in periplasmic nitrate reductase activity, suggesting that DsbB might fulfil an additional role in anaerobic electron transport. Mutants defective in dipZ (dsbD) were only slightly more sensitive to Cu⁺⁺ ions at concentrations above 5?mM than the parental strain, but strains defective in DsbA, DsbB, DsbC, DsbE or DsbF were unaffected. These results are consistent with our earlier proposals that DsbA, DsbB and DipZ (DsbD) are part of the same pathway for ensuring that haem groups are attached to the correct pairs of cysteine residues of apocytochromes c in the E. coli periplasm. However, neither DsbE nor DsbF are essential for the reduction of DipZ (DsbD).     

A cell-cycle-dependent protein of Physarum polycephalum revealed by two-dimensional gel electrophoresis.

Silver-stained two-dimensional polyacrylamide gels of Physarum polycephalum extracts have revealed no major changes in protein accumulation during the synchronous nuclear division cycle. However, one protein, or apparent Mr 32 000 and isoelectric point 4.9, shows a reproducible ten-fold increase in total amount between early G2 phase and metaphase. This protein represents about 0.005% of total plasmodial protein.     

The effects of ketone bodies,bicarbonate, and calcium on hepatic mitochondrial ketogenesis

The effect of various factors on hepatic mitochondrial ketogenesis was investigated in the rat. A comparison of three different incubation media revealed that bicarbonate ion inhibited the rate of ketone body production and decreased the ratio of 3-hydroxybutyrate/acetoacetate. The addition of 0.8 mm calcium caused significant inhibition of ketogenesis from both octanoate (40–50%) and palmitate (25–30%) and no change in the ratio of 3-hydroxybutyrate/acetoacetate. In the presence of components of the malate/aspartate shuttle, the inhibition by calcium was 80% or more with both substrates. Experimental alteration of the respiratory state of the mitochondria from state 3 to state 4 was associated with an enhanced rate of ketogenesis. The addition of ketone bodies themselves had marked effects on the rate of ketone body production. Increasing amounts of exogenously added acetoacetate were accompanied by increasing rates of total ketone body production reflecting enhanced 3-hydroxybutyrate synthesis. In the presence of added 3-hydroxybutyrate, there was striking inhibition of ketogenesis. Rotenone, which prevents oxidation of NADH₂ via the electron transport chain, almost completely inhibited ketone body synthesis. This inhibition was partially overcome by the addition of acetoacetate which regenerates NAD⁺ from NADH₂ during conversion to 3-hydroxybutyrate. These observations provide evidence for additional sites of metabolic control over hepatic ketogenesis.