Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe

A simple quasi-3D theory for static stability analysis of imperfect FG beam

This study introduces a simplified approach to assess the buckling and static bending of advanced composite beams, including those composed of functionally graded materials (FGMs) with various porosity models. The technique utilizes a straightforward integral quasi-3D approach based on the advanced shear deformation theory. This approach offers several advantages: it simplifies the analysis by reducing the number of unknowns and equations required, improves accuracy by considering the stretch effect across the entire depth of the beam, resulting in more reliable results, and accurately represents shear by satisfying the zero-traction boundary conditions on the beam’s surfaces without the need for a shear correction factor. Additionally, it captures the parabolic pattern of transverse shear strain and stress throughout the depth of the beam. The governing equations are obtained by applying the concept of virtual work, and the Navier solution is employed to calculate analytical solutions for the buckling and static bending of FGM porous beams under different boundary conditions. The approach is in line with and builds upon existing research on FGMs and other sophisticated composite beams, further enhancing its validity and reliability. Finally, computational analyses demonstrate how the distribution of materials, such as power-law functionally graded materials (FGMs), geometry, and porosity, affect the deflections, stresses, and critical buckling load of the beam

The unusual mesophases and properties exhibited by a family of glycosteroids

In this article we describe research on the synthesis and characterization of a family of “Janus” amphiphiles composed of disaccharide head groups and alkaloid units joined together via a methylene linker, and bearing a lateral aliphatic chain of varying length. The condensed phases formed by self-organization of the products as a function of temperature were characterized by differential scanning calorimetry, thermal polarized light microscopy, and small angle X-ray scattering, allied with computational modelling and simulations. Structural studies on heating specimens from the solid showed that some homologues exhibited lamellar, columnar and bicontinuous mesophases, whereas the same homologues revealed different phase sequences on cooling from the amorphous liquid. We explore these unusual results, which are revealed via supercooling

Self-organizing behaviour of glycosteroidal bolaphiles : insights into lipidic microssegregation

International audienceIn this article we describe work on the synthesis of bolaphile biomimics composed of glucose head groups and steroidal units linked together by a methylene chain of varying length. The condensed phases formed by self-organization of the products as a function of temperature were characterized by differential scanning calorimetry and thermal polarized light microscopy. The results of these studies show that the thermal stabilities of the lamellar mesophases formed vary linearly as a function of increasing aliphatic composition, which reflects a linear hydrophobic-hydrophilic balance with respect to transition temperatures

Immunocytochemical evidence for the presence of gamma 1-MSH-like immunoreactivity in pituitary corticotrophs and ACTH-producing tumours.

The presence of gamma 1-MSH has been demonstrated in bovine neuro-intermediate lobe by biochemical methods, thus suggesting that this peptide is cleaved from the cryptic region of pro-opiocortin. In this study we report the localisation of gamma 1-MSH-like immunoreactivity in the adenohypophysis of man, ox, pig, dog and guinea-pig using immunocytochemical procedures at both light and electron microscope levels. Antisera recognising the C-terminal Arg-Phe-amide and the C-terminal penta-peptide-amide of gamma 1-MSH have been used throughout this study. The immunostaining was found in all endocrine cells of the pars intermedia (where present) and in scattered cells of the pars distalis identified as corticotrophs. No gamma 1-MSH immunoreactivity was detected in rat adenohypophysis. In addition, 7 ACTH-producing tumours (1 pituitary adenoma and 6 ectopic) were investigated and shown to contain gamma 1-MSH immunoreactive cells