Comparison of 5% versus 15% sucrose intakes as part of a eucaloric diet in overweight and obese subjects:effects on insulin sensitivity, glucose metabolism, vascular compliance, body composition and lipid profile. A randomised controlled trial

AIMS: The effect of dietary sucrose on insulin resistance and the pathogenesis of diabetes and vascular disease is unclear. We assessed the effect of 5% versus 15% sucrose intakes as part of a weight maintaining, eucaloric diet in overweight/obese subjects.

METHODS: Thirteen subjects took part in a randomised controlled crossover study (M:F 9:4, median age 46 years, range 37-56 years, BMI 31.7±0.9 kg/m(2)). Subjects completed two 6 week dietary periods separated by 4 week washout. Diets were designed to have identical macronutrient profile. Insulin action was assessed using a two-step hyperinsulinaemic euglycaemic clamp; glucose tolerance, vascular compliance, body composition and lipid profiles were also assessed.

RESULTS: There was no change in weight or body composition between diets. There was no difference in peripheral glucose utilization or suppression of endogenous glucose production. Fasting glucose was significantly lower after the 5% diet. There was no demonstrated effect on lipid profiles, blood pressure or vascular compliance.

CONCLUSION: A low-sucrose diet had no beneficial effect on insulin resistance as measured by the euglycaemic glucose clamp. However, reductions in fasting glucose, one hour insulin and insulin area under the curve with the low sucrose diet on glucose tolerance testing may indicate a beneficial effect and further work is required to determine if this is the case. Clinical Trial Registration number ISRCTN50808730.

Arene cis-Diol Dehydrogenase-Catalysed Regio- and Stereoselective Oxidation of Arene-, Cycloalkane- and Cycloalkene-cis-diols to Yield Catechols and Chiral α-Ketols

Benzene cis-diol dehydrogenase and naphthalene cis-diol dehydrogenase enzymes, expressed in Pseudomonas putida wild-type and Escherichia coli recombinant strains, were used to investigate regioselectivity and stereoselectivity during dehydrogenations of arene, cyclic alkane and cyclic alkene vicinal cis-diols. The dehydrogenase-catalysed production of enantiopure cis-diols, α-ketols and catechols, using benzene cis-diol dehydrogenase and naphthalene cis-diol dehydrogenase, involved both kinetic resolution and asymmetric synthesis methods. The chemoenzymatic production and applications of catechol bioproducts in synthesis were investigated.

The association between glucose lowering drug use and mortality among breast cancer patients with type 2 diabetes.

This study assessed the association between glucose-lowering drug (GLD) use, including metformin, sulphonylurea derivatives and insulin, after breast cancer diagnosis and breast cancer-specific and all-cause mortality. 1763 breast cancer patients, diagnosed between 1998 and 2010, with type 2 diabetes were included. Cancer information was retrieved from English cancer registries, prescription data from the UK Clinical Practice Research Datalink and mortality data from the Office of National Statistics (up to January 2012). Time-varying Cox regression models were used to calculate HRs and 95 % CIs for the association between GLD use and breast cancer-specific and all-cause mortality. In 1057 patients with diabetes before breast cancer, there was some evidence that breast cancer-specific mortality decreased with each year of metformin use (adjusted HR 0.88; 95 % CI 0.75–1.04), with a strong association seen with over 2 years of use (adjusted HR 0.47; 95 % CI 0.26–0.82). Sulphonylurea derivative use for less than 2 years was associated with increased breast cancer-specific mortality (adjusted HR 1.70; 95 % CI 1.18–2.46), but longer use was not (adjusted HR 0.94; 95 % CI 0.54–1.66). In 706 patients who developed diabetes after breast cancer, similar patterns were seen for metformin, but sulphonylurea derivative use was strongly associated with cancer-specific mortality (adjusted HR 3.64; 95 % CI 2.16–6.16), with similar estimates for short- and long-term users. This study provides some support for an inverse association between, mainly long-term, metformin use and (breast cancer-specific) mortality. In addition, sulphonylurea derivative use was associated with increased breast cancer-specific mortality, but this should be interpreted cautiously, as it could reflect selective prescribing in advanced cancer patients.

Small GTPase RhoA and its effector rho kinase mediate oxygen glucose deprivation-evoked in vitro cerebral barrier dysfunction

BACKGROUND AND PURPOSE: Enhanced vascular permeability attributable to disruption of blood-brain barrier results in the development of cerebral edema after stroke. Using an in vitro model of the brain barrier composed of human brain microvascular endothelial cells and human astrocytes, this study explored whether small GTPase RhoA and its effector protein Rho kinase were involved in permeability changes mediated by oxygen-glucose deprivation (OGD), key pathological phenomena during ischemic stroke.

METHODS: OGD increased RhoA and Rho kinase protein expressions in human brain microvascular endothelial cells and human astrocytes while increasing or unaffecting that of endothelial nitric oxide synthase in respective cells. Reperfusion attenuated the expression and activity of RhoA and Rho kinase in both cell types compared to their counterparts exposed to equal periods of OGD alone while selectively increasing human brain microvascular endothelial cells endothelial nitric oxide synthase protein levels. OGD compromised the barrier integrity as confirmed by decreases in transendothelial electric resistance and concomitant increases in flux of permeability markers sodium fluorescein and Evan's blue albumin across cocultures. Transfection of cells with constitutively active RhoA also increased flux and reduced transendothelial electric resistance, whereas inactivation of RhoA by anti-RhoA Ig electroporation exerted opposite effects. In vitro cerebral barrier dysfunction was accompanied by myosin light chain overphosphorylation and stress fiber formation. Reperfusion and treatments with a Rho kinase inhibitor Y-27632 significantly attenuated barrier breakdown without profoundly altering actin structure.

CONCLUSIONS: Increased RhoA/Rho kinase/myosin light chain pathway activity coupled with changes in actin cytoskeleton account for OGD-induced endothelial barrier breakdown.