Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3) GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-diabetes.

Glucose-dependent insulinotropic polypeptide (gastric inhibitory polypeptide [GIP]) is an important incretin hormone secreted by endocrine K-cells in response to nutrient ingestion. In this study, we investigated the effects of chemical ablation of GIP receptor (GIP-R) action on aspects of obesity-related diabetes using a stable and specific GIP-R antagonist, (Pro3)GIP. Young adult ob/ob mice received once-daily intraperitoneal injections of saline vehicle or (Pro3)GIP over an 11-day period. Nonfasting plasma glucose levels and the overall glycemic excursion (area under the curve) to a glucose load were significantly reduced (1.6-fold; P <0.05) in (Pro3)GIP-treated mice compared with controls. GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P <0.05) and insulin (1.5-fold; P <0.05) responses to feeding. These changes were associated with significantly enhanced (1.6-fold; P <0.05) insulin sensitivity in the (Pro3)GIP-treated group. Daily injection of (Pro3)GIP reduced pancreatic insulin content (1.3-fold; P <0.05) and partially corrected the obesity-related islet hypertrophy and ß-cell hyperplasia of ob/ob mice. These comprehensive beneficial effects of (Pro3)GIP were reversed 9 days after cessation of treatment and were independent of food intake and body weight, which were unchanged. These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes.

Europeanization, Conditionality and Domestic Change: The Twinning Exercise and Administrative Reform in Romania

A key requirement of the countries of central and eastern Europe (CEECs) that wish to join the EU is that they develop the administrative capacity to implement effectively the acquis communautaire. The 'twinning' programme is designed to assist in this process. Drawing on experiences in Romania, and linking these to debates on Europeanization, this article argues that the success of twinning to date is related to the design of the programme, institutional fluidity and politicization within central administration, the individual agency and the reform commitment of those hosting twinning projects.

An investigation of the thermal stability and sulphur tolerance of Ag/Y-Al2O3 catalysts for the SCR of NOx with hydrocarbons and hydrogen

The sulphur tolerance and thermal stability of a 2 wt% Ag/gamma-Al2O3 catalyst was investigated for the H-2-promoted SCR of NO, with octane and toluene. The aged catalyst was characterised by XRD and EXAFS analysis. It was found that the effect of ageing was a function of the gas mix and temperature of ageing. At high temperatures (800 degrees C) the catalyst deactivated regardless of the reaction mix. EXAFS analysis showed that this was associated with the Ag particles on the surface of the catalyst becoming more ordered. At 600 and 700 degrees C, the deactivating effect of ageing was much less pronounced for the catalyst in the H-2-promoted octane-SCR reaction and ageing at 600 degrees C resulted in an enhancement in activity for the reaction in the absence of H-2. For the toluene + H-2-SCR reaction the catalyst deactivated at each ageing temperature. The effect of addition of low levels of sulphur (1 ppm SO2) to the feed was very much dependent on the reaction temperature. There was little deactivation of the catalyst at low temperatures ( 500 degrees C). The results can be explained by the activity of the catalyst for the oxidation Of SO2 to SO3 and the relative stability of silver and aluminium sulphates. The catalyst could be almost fully regenerated by a combination of heating and the presence of hydrogen in the regeneration mix. The catalyst could not be regenerated in the absence of hydrogen. (c) 2006 Published by Elsevier B.V.

Randomised controlled trial of home-based walking programmes at and below current recommended levels of exercise in sedentary adults

Objectives: To determine, using unsupervised walking programmes, the effects of exercise at a level lower than currently recommended to improve cardiovascular risk factors and functional capacity.

High tolerance to gate misalignment in low voltage gate-underlap double gate MOSFETs

.In this letter, we demonstrate for the first time that gate misalignment is not a critical limiting factor for low voltage operation in gate-underlap double gate (DG) devices. Our results show that underlap architecture significantly extends the tolerable limit of gate misalignment in 25 nm devices. DG MOSFETs with high degree of gate misalignment and optimal gate-underlap design can perform comparably or even better than self-aligned nonunderlap devices. Results show that spacer-to-straggle (s/sigma) ratio, a key design parameter for underlap devices, should be within the range of 2.3-3.0 to accommodate back gate misalignment. These results are very significant as the stringent process control requirements for achieving self-alignment in nanoscale planar DG MOSFETs are considerably relaxed