Beneficial effects of parenteral GLP-1 delivery by cell therapy in insulin-deficient streptozotocin diabetic mice.

Parenteral delivery of long-Acting glucagon-like peptide-1 (GLP-1) mimetics has received much attention as a therapeutic option for diabetes. However, cell therapy-based GLP-1 treatments may provide a more physiological regulation of blood glucose. The present study assessed the effects of chronic GLP-1 delivery by cell therapy, using the GLP-1-secreting GLUTag cell line, in normoglycemic and streptozotocin-induced diabetic mice. GLUTag cell aggregates were transplanted into the subscapular region of mice. Over 30 days, cellular transplantation gave rise to encapsulated and well-vascularized growths, which contained immunoreactive GLP-1. Cell implantation was well tolerated and had no appreciable metabolic effects in normal mice. However, transplantation significantly (P<0.001) countered excessive food and fluid intake in diabetic mice and maintained normal body weight. Circulating glucose (P<0.01) and glucagon (P<0.05) were significantly reduced and plasma insulin and GLP-1 dramatically increased. This was associated with significantly (P<0.01) improved glucose tolerance in diabetic mice. Histological examination of the pancreata of these mice revealed elevations (P<0.001) in islet and β-cell area, with reduced (P<0.001) -cell area. Increased β-cell mass reflected the enhanced proliferation relative to apoptosis. These studies emphasize the potential of chronic GLP-1 delivery by cell therapy as a potential therapeutic option for diabetes

Genomic RDA for the identification of chromosomal aberrations in pancreatic cancer: merits and in drawbacks

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In-silico Assessment of Protein-Protein Electron Transfer. A Case Study: Cytochrome c Peroxidase – Cytochrome c

<div><p>The fast development of software and hardware is notably helping in closing the gap between macroscopic and microscopic data. Using a novel theoretical strategy combining molecular dynamics simulations, conformational clustering, <i>ab-initio</i> quantum mechanics and electronic coupling calculations, we show how computational methodologies are mature enough to provide accurate atomistic details into the mechanism of electron transfer (ET) processes in complex protein systems, known to be a significant challenge. We performed a quantitative study of the ET between Cytochrome c Peroxidase and its redox partner Cytochrome c. Our results confirm the ET mechanism as hole transfer (HT) through residues Ala194, Ala193, Gly192 and Trp191 of CcP. Furthermore, our findings indicate the fine evolution of the enzyme to approach an elevated turnover rate of 5.47×10⁶ s⁻¹ for the ET between Cytc and CcP through establishment of a localized bridge state in Trp191.</p> </div

Electron transfer region of the CcP/Cytc complex.

<p>The ET pathway proposed by Pelletier and Kraut is shown in red, the ET pathway suggested by Siddarth is shown in blue.</p

Average distances <i>d</i> in Å, Electronic coupling <i>rmsV</i> in eV, Δ<i>G</i>° in eV, λ in eV and in s⁻¹ calculated for HT between donor and acceptor (DA), donor and bridge (DB), and bridge and acceptor (BA), respectively.

<p>The electronic coupling is calculated applying QM setups <i>direct</i>, <i>full</i>, <i>path1</i> and <i>path2</i>. <i>k_ET</i> is calculated by Marcus theory applying the respective highest electronic coupling of the system. Fluctuations are depicted through the coherence factor given in parentheses.</p