The adult non-obese Goto–Kakizaki (GK) rat model of type 2 diabetes, particularly females, carries in addition to hyperglycaemia a genetic predisposition towards dyslipidaemia, including hypercholesterolaemia. As cholesterol-induced atherosclerosis may be programmed in utero, we looked for signs of perinatal lipid alterations and islet microangiopathy. We hypothesise that such alterations contribute towards defective pancreas/islet vascularisation that might, in turn, lead to decreased beta cell mass. Accordingly, we also evaluated islet inflammation and endothelial activation in both prediabetic and diabetic animals.
Introduction La microangiopathie diabetique est reconnue au niveau renal et oculaire, mais pas encore au niveau de l'ilot bien qu'une reaction inflammatoire insulaire ait ete decelee chez des patients et divers modeles animaux de DT2. Chez le rat GK, l'inflammation insulaire progresse parallelement a l'hyperglycemie, qui debute au sevrage (28 j) et s'accompagne d'une alteration endotheliale et de fibrose insulaire. Les rats GK, surtout les femelles, presentent aussi une dyslipidemie. Or un lien entre perturbations metaboliques chez la mere gestante et hypertension, maladies cardiovasculaires et diabetes dans la descendance a ete etabli. Notre hypothese est que l'hyperlipidemie maternelle, associee a l'hyperglycemie, perturbe le developpement du pancreas endocrine chez le rat GK via la mise en place d'un processus de type microangiopathie/atherosclerose. Materiels et methodes Les ilots de rats males Wistar (temoins) et GK âges de 7 jours ont ete isoles. Par une double approche ( Affimetrix gene array et Oligo-GEAarray ® ) l'expression de genes en rapport avec la vascularisation (endothelium, angiogenese et maladies cardiovasculaires) a ete comparee dans les 2 groupes d'ilots. Resultats Les ilots des nouveau-nes GK (prediabetiques) 1) surexpriment des genes codant pour des facteurs proarteriosclereux : caspase 1, IL-15, IL-18, CXCL1, CXCL2, ICAM-1, fibronectine, carboxypeptidase-2 et angiotensinogene ; 2) sous-expriment des genes codant pour des molecules pro-angiogeniques : osteoprotegerine, neuropiline-1, eotaxine, PDGF-β, facteur tissulaire et neuropeptide Y, suggerant un defaut d'angiogenese ; 3) surexpriment les genes de molecules aux effets anti-arteriosclerose et vasoprotecteur : prostacycline synthetase et apolipoproteine A-1 ; 4) sous-expriment le gene de l'epoxyde hydrolase (EH) qui, en augmentant le taux des acides epoxyeicosatrienoiques, prolonge les effets vasodilateur, anti-inflammatoire, anti-oxydant et angiogenique d'autres facteurs. Le gene de l'EH est aussi sous-exprime dans le pancreas du rat GK au stade fœtal. Conclusion Chez le rat GK des processus pro-inflammatoires (proarteriosclereux) et anti-inflammatoires au niveau de l'endothelium insulaire sont en place des la periode perinatale. L'alteration vasculaire insulaire pourrait etre a l'origine du deficit precoce en cellules β pancreatiques observe chez ces animaux.
This article comprises the first part of a study concerning the effect that a flow of gaseous He-4 has on the concentration distribution of He-3 atoms in the presence of a superfluid film. We present a simple model in which hydrodynamic effects in the gas phase (diffusion and viscosity), and local thermodynamic equilibrium with a superfluid film are considered. Results are derived and discussed for the simple case in which a heat flow is sustained along a cylindrical tube lined with a helium film. This heat flux drives a superfluid flow in the film, and a corresponding counterflow of He-4 in the vapour. The pressure, temperature, He-3 concentration, and film thickness profiles along the tube are computed. Over a wide range of conditions, a dramatic reduction of the He-3 concentration, a large temperature increase, and a spectacular film thinning towards hotter regions are predicted to result from a heat flow. The results of a series of experiments supporting this model will be presented in a forthcoming article.
We report the results of pressure, temperature, and isotopic concentration measurements in tubes lined with a thermally driven, flowing superfluid film. For pure4He films, vapour refluxing generates gradients in both pressure and temperature. With the addition of a few percent of3He, pressure gradients are dramatically reduced and the refluxing of4He atoms in the vapour couples gradients in temperature and isotopic concentration. We have observed that the3He concentration at the hot end of a narrow tube can be decreased by a factor greater than 104. These results can be interpreted in terms of a recently developed model which includes a description of the hydrodynamics of the refluxing vapour.
This article comprises the first part of a study concerning the effect that a flow of gaseous4He has on the concentration distribution of3He atoms in the presence of a super fluid film. We present a simple model in which hydrodynamic effects in the gas phase (diffusion and viscosity), and local thermodynamic equilibrium with a superfluid film are considered. Results are derived and discussed for the simple case in which a heat flow is sustained along a cylindrical tube lined with a helium film. This heat flux drives a superfluid flow in the film, and a corresponding counterflow of4He in the vapour. The pressure, temperature,3He concentration, and film thickness profiles along the tube are computed. Over a wide range of conditions, a dramatic reduction of the3He concentration, a large temperature increase, and a spectacular film thinning towards hotter regions are predicted to result from a heat flow. The results of a series of experiments supporting this model will be presented in a forthcoming article.
We have prepared a large sample of spin polarized liquid 3 He- 4 He at 500 mK. Polarization is obtained by laser optical pumping, and studied by pulsed NMR. We have observed a nuclear magnetization lifetime T 1 longer than 1 hour, and an anomalously long, non linear decay of tranverse magnetization.
We describe the design and construction of a dilution refrigerator to obtain polarized liquid 3 He in the degenerate region by liquifying and cooling optically pumped gas. This apparatus will extend the temperature region accessible with a 3He cryostat for the study of polarized 'He in our group (1). To establish thermal contact between the mixing chamber and the sample we have designed a non-magnetic heat switch, based on the large thermal conductivity of liquid 4He.