118 research outputs found
Wholegrain fermentation affects gut microbiota composition, phenolic acid metabolism and pancreatic beta cell function in a rodent model of type 2 diabetes
The intestinal microbiota plays an important role in host metabolism via production of dietary metabolites. Microbiota imbalances are linked to type 2 diabetes (T2D), but dietary modification of the microbiota may promote glycemic control. Using a rodent model of T2D and an in vitro gut model system, this study investigated whether differences in gut microbiota between control mice and mice fed a high-fat, high-fructose (HFHFr) diet influenced the production of phenolic acid metabolites following fermentation of wholegrain (WW) and control wheat (CW). In addition, the study assessed whether changes in metabolite profiles affected pancreatic beta cell function. Fecal samples from control or HFHFr-fed mice were fermented in vitro with 0.1% (w/v) WW or CW for 0, 6, and 24 h. Microbiota composition was determined by bacterial 16S rRNA sequencing and phenolic acid (PA) profiles by UPLC-MS/MS. Cell viability, apoptosis and insulin release from pancreatic MIN6 beta cells and primary mouse islets were assessed in response to fermentation supernatants and selected PAs. HFHFr mice exhibited an overall dysbiotic microbiota with an increase in abundance of proteobacterial taxa (particularly Oxalobacteraceae) and Lachnospiraceae, and a decrease in Lactobacillus. A trend toward restoration of diversity and compositional reorganization was observed following WW fermentation at 6 h, although after 24 h, the HFHFr microbiota was monodominated by Cupriavidus. In parallel, the PA profile was significantly altered in the HFHFr group compared to controls with decreased levels of 3-OH-benzoic acid, 4-OH-benzoic acid, isoferulic acid and ferulic acid at 6 h of WW fermentation. In pancreatic beta cells, exposure to pre-fermentation supernatants led to inhibition of insulin release, which was reversed over fermentation time. We conclude that HFHFr mice as a model of T2D are characterized by a dysbiotic microbiota, which is modulated by the in vitro fermentation of WW. The differences in microbiota composition have implications for PA profile dynamics and for the secretory capacity of pancreatic beta cells
Somatostatin Secreted by Islet δ-Cells Fulfills Multiple Roles as a Paracrine Regulator of Islet Function
OBJECTIVE— Somatostatin (SST) is secreted by islet δ-cells and by extraislet neuroendocrine cells. SST receptors have been identified on α- and β-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating α- and β-cell function. However, the specific intraislet function of δ-cell SST remains uncertain. We have used Sst−/− mice to investigate the role of δ-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo
Geometry dominated fluid adsorption on sculptured substrates
Experimental methods allow the shape and chemical composition of solid
surfaces to be controlled at a mesoscopic level. Exposing such structured
substrates to a gas close to coexistence with its liquid can produce quite
distinct adsorption characteristics compared to that occuring for planar
systems, which may well play an important role in developing technologies such
as super-repellent surfaces or micro-fluidics. Recent studies have concentrated
on adsorption of liquids at rough and heterogeneous substrates and the
characterisation of nanoscopic liquid films. However, the fundamental effect of
geometry has hardly been addressed. Here we show that varying the shape of the
substrate can exert a profound influence on the adsorption isotherms allowing
us to smoothly connect wetting and capillary condensation through a number of
novel and distinct examples of fluid interfacial phenomena. This opens the
possibility of tailoring the adsorption properties of solid substrates by
sculpturing their surface shape.Comment: 6 pages, 4 figure
Chaotic Properties of Dilute Two and Three Dimensional Random Lorentz Gases I: Equilibrium Systems
We compute the Lyapunov spectrum and the Kolmogorov-Sinai entropy for a
moving particle placed in a dilute, random array of hard disk or hard sphere
scatterers - i.e. the dilute Lorentz gas model. This is carried out in two
ways: First we use simple kinetic theory arguments to compute the Lyapunov
spectrum for both two and three dimensional systems. In order to provide a
method that can easily be generalized to non-uniform systems we then use a
method based upon extensions of the Lorentz-Boltzmann (LB) equation to include
variables that characterize the chaotic behavior of the system. The extended LB
equations depend upon the number of dimensions and on whether one is computing
positive or negative Lyapunov exponents. In the latter case the extended LB
equation is closely related to an "anti-Lorentz-Boltzmann equation" where the
collision operator has the opposite sign from the ordinary LB equation. Finally
we compare our results with computer simulations of Dellago and Posch and find
very good agreement.Comment: 48 pages, 3 ps fig
Structural basis for delta cell paracrine regulation in pancreatic islets
International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions
Interface localisation-delocalisation transition in a symmetric polymer blend: a finite-size scaling Monte Carlo study
Using extensive Monte Carlo simulations we study the phase diagram of a
symmetric binary (AB) polymer blend confined into a thin film as a function of
the film thickness D. The monomer-wall interactions are short ranged and
antisymmetric, i.e, the left wall attracts the A-component of the mixture with
the same strength as the right wall the B-component, and give rise to a first
order wetting transition in a semi-infinite geometry. The phase diagram and the
crossover between different critical behaviors is explored. For large film
thicknesses we find a first order interface localisation/delocalisation
transition and the phase diagram comprises two critical points, which are the
finite film width analogies of the prewetting critical point. Using finite size
scaling techniques we locate these critical points and present evidence of 2D
Ising critical behavior. When we reduce the film width the two critical points
approach the symmetry axis of the phase diagram and for we encounter a tricritical point. For even smaller film thickness the
interface localisation/delocalisation transition is second order and we find a
single critical point at .
Measuring the probability distribution of the interface position we determine
the effective interaction between the wall and the interface. This effective
interface potential depends on the lateral system size even away from the
critical points. Its system size dependence stems from the large but finite
correlation length of capillary waves. This finding gives direct evidence for a
renormalization of the interface potential by capillary waves in the framework
of a microscopic model.Comment: Phys.Rev.
Nephrin Is Expressed on the Surface of Insulin Vesicles and Facilitates Glucose-Stimulated Insulin Release
Nephrin, an immunoglobulin-like protein essential for the function of the glomerular podocyte and regulated in diabetic nephropathy, is also expressed in pancreatic beta-cells, where its function remains unknown. The aim of this study was to investigate whether diabetes modulates nephrin expression in human pancreatic islets and to explore the role of nephrin in beta-cell function.
Nephrin expression in human pancreas and in MIN6 insulinoma cells was studied by Western blot, PCR, confocal microscopy, subcellular fractionation, and immunogold labeling. Islets from diabetic (n = 5) and nondiabetic (n = 7) patients were compared. Stable transfection and siRNA knockdown in MIN-6 cells/human islets were used to study nephrin function in vitro and in vivo after transplantation in diabetic immunodeficient mice. Live imaging of green fluorescent protein (GFP)-nephrin-transfected cells was used to study nephrin endocytosis.
Nephrin was found at the plasma membrane and on insulin vesicles. Nephrin expression was decreased in islets from diabetic patients when compared with nondiabetic control subjects. Nephrin transfection in MIN-6 cells/pseudoislets resulted in higher glucose-stimulated insulin release in vitro and in vivo after transplantation into immunodeficient diabetic mice. Nephrin gene silencing abolished stimulated insulin release. Confocal imaging of GFP-nephrin-transfected cells revealed nephrin endocytosis upon glucose stimulation. Actin stabilization prevented nephrin trafficking as well as nephrin-positive effect on insulin release.
Our data suggest that nephrin is an active component of insulin vesicle machinery that may affect vesicle-actin interaction and mobilization to the plasma membrane. Development of drugs targeting nephrin may represent a novel approach to treat diabetes
Lattice Boltzmann simulations of soft matter systems
This article concerns numerical simulations of the dynamics of particles
immersed in a continuum solvent. As prototypical systems, we consider colloidal
dispersions of spherical particles and solutions of uncharged polymers. After a
brief explanation of the concept of hydrodynamic interactions, we give a
general overview over the various simulation methods that have been developed
to cope with the resulting computational problems. We then focus on the
approach we have developed, which couples a system of particles to a lattice
Boltzmann model representing the solvent degrees of freedom. The standard D3Q19
lattice Boltzmann model is derived and explained in depth, followed by a
detailed discussion of complementary methods for the coupling of solvent and
solute. Colloidal dispersions are best described in terms of extended particles
with appropriate boundary conditions at the surfaces, while particles with
internal degrees of freedom are easier to simulate as an arrangement of mass
points with frictional coupling to the solvent. In both cases, particular care
has been taken to simulate thermal fluctuations in a consistent way. The
usefulness of this methodology is illustrated by studies from our own research,
where the dynamics of colloidal and polymeric systems has been investigated in
both equilibrium and nonequilibrium situations.Comment: Review article, submitted to Advances in Polymer Science. 16 figures,
76 page
Amelioration of Streptozotocin-Induced Diabetes in Mice with Cells Derived from Human Marrow Stromal Cells
Pluri-potent bone marrow stromal cells (MSCs) provide an attractive opportunity to generate unlimited glucose-responsive insulin-producing cells for the treatment of diabetes. We explored the potential for human MSCs (hMSCs) to be differentiated into glucose-responsive cells through a non-viral genetic reprogramming approach.Two HMSC lines were transfected with three genes: PDX-1, NeuroD1 and Ngn3 without subsequent selection, followed by differentiation induction in vitro and transplantation into diabetic mice. Human MSCs expressed mRNAs of the archetypal stem cell markers: Sox2, Oct4, Nanog and CD34, and the endocrine cell markers: PDX-1, NeuroD1, Ngn3, and Nkx6.1. Following gene transfection and differentiation induction, hMSCs expressed insulin in vitro, but were not glucose regulated. After transplantation, hMSCs differentiated further and approximately 12.5% of the grafted cells expressed insulin. The graft bearing kidneys contained mRNA of insulin and other key genes required for the functions of beta cells. Mice transplanted with manipulated hMSCs showed reduced blood glucose levels (from 18.9+/-0.75 to 7.63+/-1.63 mM). 13 of the 16 mice became normoglycaemic (6.9+/-0.64 mM), despite the failure to detect the expression of SUR1, a K(+)-ATP channel component required for regulation of insulin secretion.Our data confirm that hMSCs can be induced to express insulin sufficient to reduce blood glucose in a diabetic mouse model. Our triple gene approach has created cells that seem less glucose responsive in vitro but which become more efficient after transplantation. The maturation process requires further study, particularly the in vivo factors influencing the differentiation, in order to scale up for clinical purposes
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