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Chemical Methods to Induce Beta-Cell Proliferation
Full text linkPancreatic beta-cell regeneration, for example, by inducing proliferation, remains an important goal in developing effective treatments for diabetes. However, beta cells have mainly been considered quiescent. This “static” view has recently been challenged by observations of relevant physiological conditions in which metabolic stress is compensated by an increase in beta-cell mass. Understanding the molecular mechanisms underlining these process could open the possibility of developing novel small molecules to increase beta-cell mass. Several cellular cell-cycle and signaling proteins provide attractive targets for high throughput screening, and recent advances in cell culture have enabled phenotypic screening for small molecule-induced beta-cell proliferation. We present here an overview of the current trends involving small-molecule approaches to induce beta-cell regeneration by proliferation
All-transglycolytic synthesis and characterisation of sialyl(alfa2-3)galactosyl(beta1-4)xylosyl-p-nitrophenyl(beta1-, an oligosaccharide derivative related to glycosaminoglycans biosynthesis
No full textEnzymatic Synthesis and Characterization of Oligosaccharides Structurally Related to the Repeating Unit of Pullulan
No full textA trisaccharide (Glca1–4Glca1–6Glc) and a tetrasaccharide (Glca1–4Glca1–4Glca1–6Glc) the structures of which are related
to that of repeating unit of pullulan have been obtained, exploiting the transglycolytic activity of Aspergillus niger cyclodextrin
glucanotransferase. Bothproducts were obtained in one-pot reaction using as a donor the a-cyclodextrin and as an acceptor the
disaccharide isomaltose. The regioselectivity of the reaction was 85% for the tetrasaccharide and 80% for the trisaccharide. The
yield of reaction resulted to be 42% for the synthesis of trisaccharide and 25% for that of tetrasaccharide. Purification of
products was performed by size exclusion chromatography and by semipreparative reverse phase HPLC after reversible
derivatization with 2-aminopyridine. Structural characterization was performed by capillary electrophoresis, ion-spray mass
spectrometry, and by
13
C-NMR spectroscopy. A comparison of these results with those obtained by using a-D-glucosidase,
which had been effective for the synthesis of the disaccharide isomaltose, is reported
Synthesis, Characterization, and Preliminary Biological Study of Glycoconjugates of Poly(styrene-co-maleic acid)
No full textEnzymatic synthesis and characterization of 6-O-beta-D-xylopyranosyl-2-acetamido-2-deoxy-D-glucopyranose, a structural analog of primeverose, a biologically relevant disaccharide
No full textTargeting the pancreatic β-cell to treat diabetes
No full textDiabetes is a leading cause of morbidity and mortality worldwide, and predicted to affect over 500 million people by 2030. However, this growing burden of disease has not been met with a comparable expansion in therapeutic options. The appreciation of the pancreatic β-cell as a central player in the pathogenesis of both type 1 and type 2 diabetes has renewed focus on ways to improve glucose homeostasis by preserving, expanding and improving the function of this key cell type. Here, we provide an overview of the latest developments in this field, with an emphasis on the most promising strategies identified to date for treating diabetes by targeting the β-cell
“cAMP-response element modulator-τ activates a distinct promoter element for the expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene”
No full textPHGPx (phospholipid hydroperoxide glutathione peroxidase) is a
selenoprotein present in at least three isoforms in testis: cytosolic,
mitochondrial and nuclear. All of these derive from the same gene
and are structurally related with the exception of the snPHGPx
(sperm nucleus-specific form), which differs from the others
due to the presence of an arginine-rich N-terminus. It has been
demonstrated recently that this N-terminus is encoded by an alternative
exon located in the first intron of the PHGPx gene. The
expression of snPHGPx has been attributed either to an alternative
pre-mRNA splicing or to the presence of a distinct promoter region.
Nevertheless, the exact molecular mechanism by which the
expression of snPHGPx occurs has not been demonstrated so far.
Preliminary sequence analysis of the region located upstream of
the alternative exon revealed some potential DNA-binding sites,
one of which is specific to the binding of CREM (cAMP-response
elementmodulator) transcription factors. By using electrophoretic
mobility-shift assays, we demonstrated that both nuclear protein
extract from highly purified rat spermatid cells and recombinant
CREM-τ protein can specifically bind to this element. Furthermore,
we cloned a 1059 bp comprising the intron and the alternative
exon for snPHGPx in the pCAT®3 reporter vector. By
transient transfection experiments, we demonstrated that the expression
of the transcription factor CREM-τ can induce the activation
of the reporter gene in NIH-3T3 cell line. These results were
confirmed by chromatin immunoprecipitation experiments performed
on highly purified rat spermatid cells.On the basis of these
results, we demonstrate that snPHGPx expression is mediated
by the transcription factor CREM-τ , which acts as a cis-acting
element localized in the first intron of the PHGPx gene
Galactose-Substituted Alginate, 2: Conformational Aspects
No full textGalactose moieties have been introduced on the uronic groups of alginates from different sources via an
N-glycosidic bond, thus affecting the net charge on the polymer chain. The modified polymers have been
analyzed by means of viscosity and of high-performance size-exclusion chromatography combined with
refractive index multiple angle laser light scattering (HPSEC-RI-MALLS) measurements. The latter technique
enabled us to determine the molecular weight of the modified polymers, proving that the synthetic procedure
did not affect the chemical integrity of the chain. The intrinsic viscosity and the radius of gyration data
showed that the hydrodynamic properties of the polymer chain varied with the degree and the pattern of
substitution. In the presence of a relatively low galactose content (up to 19%), a decrease of the hydrodynamic
dimensions of the coil was experienced, while on increasing the degree of substitution (especially on GG
diads) a re-extension of the chain was discovered. Measurements of intrinsic viscosity at different values of
the degree of dissociation have demonstrated that this effect cannot be solely explained by the reduction of
the charge density of the polymer. Rather, it implies the occurrence of conformational changes of the chain
that are specific to the chemical nature of the site of substitution. These data have been supported by the
values of the persistence length of the natural and modified polymers obtained with the Doty-Benoit equation.
The chiro-optical properties of the modified polymers studied by means of circular dichroism (CD)
spectroscopy confirmed that conformational variations occurred to the polymeric chain upon introduction
of galactose residues
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