Effect of Rosiglitazone on Insulin Sensitivity and Body Composition in Type 2 Diabetic Patients

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes. Research Methods and Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment. Results: There was a significant improvement in glycemic control (glycosylated hemoglobin -0.7 +/- 0.7%, p less than or equal to 0.05) and an 86% increase in insulin sensitivity in the RSG group (glucose-disposal rate change from baseline: 17.5 +/- 14.5 mumol glucose/min/kg free fat mass, P < 0.05), but no significant change in the placebo group compared with baseline. Total body weight and fat mass increased (p &LE; 0.05) with RSG (2.1 +/- 2.0 kg and 1.4 +/- 1.6 kg, respectively) with 95% of the increase in adiposity occurring in nonabdominal regions. In the abdominal region, RSG increased subcutaneous fat area by 8% (25.0 +/- 28.7 cm(2), p = 0.02), did not alter intra-abdominal fat area, and reduced intrahepatic fat levels by 45% (-6.7 +/- 9.7%, concentration relative to water). Discussion: Our data indicate that RSG greatly improves insulin sensitivity in patients with type 2 diabetes and is associated with an increase in adiposity in subcutaneous but not visceral body regions.

Prediction of Golgi Type II membrane proteins based on their transmembrane domains

Motivation: A major issue in cell biology today is how distinct intracellular regions of the cell, like the Golgi Apparatus, maintain their unique composition of proteins and lipids. The cell differentially separates Golgi resident proteins from proteins that move through the organelle to other subcellular destinations. We set out to determine if we could distinguish these two types of transmembrane proteins using computational approaches. Results: A new method has been developed to predict Golgi membrane proteins based on their transmembrane domains. To establish the prediction procedure, we took the hydrophobicity values and frequencies of different residues within the transmembrane domains into consideration. A simple linear discriminant function was developed with a small number of parameters derived from a dataset of Type II transmembrane proteins of known localization. This can discriminate between proteins destined for Golgi apparatus or other locations (post-Golgi) with a success rate of 89.3% or 85.2%, respectively on our redundancy-reduced data sets.

Spatial distribution of vectors of Ross River virus and Barmah Forest virus on Russell Island, Moreton Bay, Queensland

We used a network of 20 carbon dioxide- and octenol-supplemented light traps to sample adult mosquitoes throughout Russell Island in southern Moreton Bay, south-east Queensland. Between February and April 2001, an estimated 1365 564 adult female mosquitoes were collected. In contrast to an average catch of 9754 female mosquitoes per trap night on Russell Island, reference traps set on Macleay Island and on the mainland returned average catches of 3172 and 222, respectively. On Russell Island, Ochlerotatus vigilax (Skuse), Coquillettidia linealis (Skuse), Culex annulirostris Skuse and Verrallina funerea (Theobald), known or suspected vectors of Ross River (RR) and/or Barmah Forest (BF) viruses, comprised 89.6% of the 25 taxa collected. When the spatial distributions of the above species were mapped and analysed using local spatial statistics, all were found to be present in highest numbers towards the southern end of the island during most of the 7 weeks. This indicated the presence of more suitable adult harbourage sites and/or suboptimal larval control efficacy. As immature stages and the breeding habitat of Cq. linealis are as yet undescribed, this species in particular presents a considerable impediment to proposed development scenarios. The method presented here of mapping the numbers of mosquitoes throughout a local government area allows specific areas that have high vector numbers to be defined.

Vector competence of Coquillettidia linealis (Skuse) (Diptera : Culicidae) for Ross River and Barmah Forest viruses

Coquillettidia linealis is a severe pest on some of the Moreton Bay islands in Queensland, Australia, but little is known of its breeding habitats and biology. Because of its high abundance and its association with Ross River (RR) and Barmah Forest (BF) viruses by field isolation, its vector competence was evaluated in the laboratory by feeding dilutions of both viruses in blood. For RR, Cq. linealis was of comparable efficiency to Ochlerotatus vigilax (Skuse), recognised as being a major vector. Results were as follows for Cq. linealis and Oc. vigilax , respectively: dose to infect 50%, 10(2.2) and

Class benefits of AT1 antagonists in Type 2 diabetes with nephropathy

Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT1) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was ~ 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT1 antagonists. These clinical trials suggest that there may be a class renoprotective action with AT1 antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT1 antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.

Metformin & lifestyle intervention prevent Type 2 diabetes: lifestyle intervention has the greater effect

Diabetes mellitus is now occurring in epidemic proportions in many countries. Owing to the limited effectiveness of drug prophylaxis of diabetic complications after diabetes has developed, it may be more appropriate to investigate ways to prevent the onset of diabetes. A recent trial published by the Diabetes Prevention Programme Research Group investigated whether lifestyle changes or metformin were effective in delaying the onset of diabetes in subjects with impaired glucose tolerance. The goals of the intensive lifestyle intervention were to achieve and maintain a weight reduction of 7% through a low-calorie, low-fat diet and to engage in physical activity of moderate intensity, such as brisk walking, for at least 150 min/week. The effectiveness of the intensive lifestyle intervention on body weight was initially quite good but decreased over time. Metformin caused some weight loss but to a lesser extent than the intensive lifestyle intervention. Both therapies decreased the fasting plasma glucose levels to a similar extent initially. The intensive lifestyle intervention decreased plasma glycosylated haemoglobin levels to a greater extent than metformin. Both intensive lifestyle intervention and metformin reduced the incidence of diabetes, with the lifestyle intervention having the greater effect.

Prolonged retention after aggregation into secretory granules of human R183H-growth hormone (GH), a mutant that causes autosomal dominant GH deficiency type II

Human R183H-GH causes autosomal dominant GH deficiency type II. Because we show here that the mutant hormone is fully bioactive, we have sought to locate an impairment in its progress through the secretory pathway as assessed by pulse chase experiments. Newly synthesized wild-type and R183H-GH were stable when expressed transiently in AtT20 cells, and both formed equivalent amounts of Lubrol-insoluble aggregates within 40 min after synthesis. There was no evidence for intermolecular disulfide bond formation in aggregates of wild-type hormone or the R183H mutant. Both wildtype and R183H-GH were packaged into secretory granules, assessed by the ability of 1 mm BaCl2 to stimulate release and by immunocytochemistry. The mutant differed from wildtype hormone in its retention in the cells after packaging into secretory granules; 50% more R183H-GH than wild-type aggregates were retained in AtT20 cells 120 min after synthesis, and stimulated release of R183H-GH or a mixture of R183H-GH and wild-type that had been retained in the cell was reduced. The longer retention of R183H-GH aggregates indicates that a single point mutation in a protein contained in secretory granules affects the rate of secretory granule release.

delta N-15 values of tropical savanna and monsoon forest species reflect root specialisations and soil nitrogen status

A large number of herbaceous and woody plants from tropical woodland, savanna, and monsoon forest were analysed to determine the impact of environmental factors (nutrient and water availability, fire) and biological factors (microbial associations, systematics) on plant delta(15)N values. Foliar delta(15)N values of herbaceous and woody species were not related to growth form or phenology, but a strong relationship existed between mycorrhizal status and plant delta(15)N. In woodland and savanna, woody species with ectomycorrhizal (ECM) associations and putative N-2-fixing species with ECM/arbuscular (AM) associations had lowest foliar delta(15)N values (1.0-0.6parts per thousand), AM species had mostly intermediate delta(15)N values (average +0.6parts per thousand), while non-mycorrhizal Proteaceae had highest delta(15)N values (+2.9 to +4.1parts per thousand). Similar differences in foliar delta(15)N were observed between AM (average 0.1 and 0.2parts per thousand) and non-mycorrhizal (average +0.8 and +0.3parts per thousand) herbaceous species in woodland and savanna. Leguminous savanna species had significantly higher leaf N contents (1.8-2.5% N) than non-fixing species (0.9-1.2% N) indicating substantial N acquisition via N-2 fixation. Monsoon forest species had similar leaf N contents (average 2.4% N) and positive delta(15)N values (+0.9 to +2.4parts per thousand). Soil nitrification and plant NO3- use was substantially higher in monsoon forest than in woodland or savanna. In the studied communities, higher soil N content and nitrification rates were associated with more positive soil delta(15)N and plant delta(15)N. In support of this notion, Ficus, a high NO3- using taxa associated with NO3- rich sites in the savanna, had the highest delta(15)N values of all AM species in the savanna. delta(15)N of xylem sap was examined as a tool for studying plant delta(15)N relations. delta(15)N of xylem sap varied seasonally and between differently aged Acacia and other savanna species. Plants from annually burnt savanna had significantly higher delta(15)N values compared to plants from less frequently burnt savanna, suggesting that foliar N-15 natural abundance could be used as marker for assessing historic fire regimes. Australian woodland and savanna species had low leaf delta(15)N and N content compared to species from equivalent African communities indicating that Australian biota are the more N depauperate. The largest differences in leaf delta(15)N occurred between the dominant ECM Australian and African savanna (miombo) species, which were depleted and enriched in N-15, respectively. While the depleted delta(15)N of Australian ECM species are similar to those of previous reports on ECM species in natural plant communities, the N-15-enriched delta(15)N of African ECM species represent an anomaly.

Nitrogen use strategies of neotropical rainforest trees in threatened Atlantic Forest

The characteristics of nitrogen acquisition, transport and assimilation were investigated in species of an Atlantic Forest succession over calcareous soil in south-eastern Brazil. Differences in behaviour were observed within the regeneration guilds. Pioneer species showed high leaf nitrogen contents, a high capacity to respond to increased soil nitrogen availability, a high capacity for leaf nitrate assimilation and were characterized by the transport of nitrate + asparagine. At the other end of the succession, late secondary species had low leaf nitrogen contents, little capacity to respond to increased soil nitrogen availability, low leaf nitrate assimilation and were active in the transport of asparagine + arginine. The characteristics of nitrogen nutrition in some early secondary species showed similarities to those of pioneer species whereas others more closely resembled late secondary species. Average leaf delta(15)N values increased along the successional gradient. The results indicate that the nitrogen metabolism characteristics of species may be an additional ecophysiological tool in classifying tropical forest tree species into ecological guilds, and may have implications for regeneration programmes in degraded areas.

Conductivity/microstructure study of a pyrochlore-type ordered phase in the compound Zr0.75Ce0.08Nd0.17O1.92

The compound Zr0.75Ce0.08Nd0.17O1.92 was investigated as part of a much larger electrical conductivity/microstructure study of the systems ZrO2-CeO2-M2O3 (where M=Nd, Sm, ..., Yb) [Solid State Ionics (2002)]. Electrical conductivity measurements performed in air at 800 degreesC showed significant conductivity degradation over a period of 200 h. Investigation of the annealed and as-fired specimens by ATEM revealed the presence of an emerging, ordered pyrochlore-type phase within the Zr0.75Ce0.08Nd0.17O1.92 defect-fluorite solid solution at much lower dopant levels than observed previously for zirconia binary systems. (C) 2002 Elsevier Science B.V. All rights reserved.

Leaf area development of ABA-deficient and wild-type peas at two levels of nitrogen supply

The ABA-deficient wilty pea (Pisum sativum L.) and its wild-type (WT) were grown at two levels of nitrogen supply (0.5 and 5.0 mM) for 5-6 weeks from sowing, to determine whether leaf ABA status altered the leaf growth response to N deprivation. Plants were grown at high relative humidity to prevent wilting of the wilty peas. Irrespective of N supply, expanding wilty leaflets had ca 50% less ABA than WT leaflets but similar ethylene evolution rates. Fully expanded wilty leaflets had lower relative water contents (RWC) and were 10-60% smaller in area (according to the node of measurement) than WT leaflets. However, there were no genotypic differences in plant relative leaf expansion rate (RLER). Growth of both genotypes at 0.5 mM N increased the RWC of fully expanded leaflets, but did not alter ethylene evolution or ABA concentration of expanding leaflets. Plants grown at 0.5 mM N showed a 20-30% reduction in RLER, which was similar in magnitude in both wilty and WT peas. Thus, leaf ABA status did not alter the leaf growth response to N deprivation.