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- Davani, B, et al.
(author)
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Aged transgenic mice with increased glucocorticoid sensitivity in pancreatic beta-cells develop diabetes
- 2004
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 5353 Suppl 1, s. S51-S59
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Journal article (peer-reviewed)abstract
- Glucocorticoids are diabetogenic hormones because they decrease glucose uptake, increase hepatic glucose production, and inhibit insulin release. To study the long-term effects of increased glucocorticoid sensitivity in β-cells, we studied transgenic mice overexpressing the rat glucocorticoid receptor targeted to the β-cells using the rat insulin I promoter. Here we report that these mice developed hyperglycemia both in the fed and the overnight-fasted states at 12–15 months of age. Progression from impaired glucose tolerance, previously observed in the same colony at the age of 3 months, to manifest diabetes was not associated with morphological changes or increased apoptosis in the β-cells. Instead, our current results suggest that the development of diabetes is due to augmented inhibition of insulin secretion through α2-adrenergic receptors (α2-ARs). Thus, we found a significantly higher density of α2-ARs in the islets of transgenic mice compared with controls, based on binding studies with the α2-AR agonist UK 14304. Furthermore, incubation of islets with benextramine, a selective antagonist of the α2-AR, restored insulin secretion in response to glucose in isolated islets from transgenic mice, whereas it had no effect on control islets. These results indicate that the chronic enhancement of glucocorticoid signaling in pancreatic β-cells results in hyperglycemia and impaired glucose tolerance. This effect may involve signaling pathways that participate in the regulation of insulin secretion via the α2-AR.
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- D'Errico, G, et al.
(author)
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Temperature and concentration effects on supramolecular aggregation and phase behavior for poly(propylene oxide)-b-poly(ethylene oxide)-b-poly(propylene oxide) copolymers of different composition in aqueous mixtures, 1
- 2004
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In: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 279:2, s. 379-390
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Journal article (peer-reviewed)abstract
- The phase behavior (temperature vs composition) and microstructure for the two binary systems Pluronic 25R4 [(PO)(19)(EO)33(PO)(19)]-water and Pluronic 25R2 [PO)(21)(EO)(14)(PO)(21)]-water have been studied by a combined experimental approach in the whole concentration range and from 5 to 80 degreesC. The general phase behavior has been identified by inspection under polarized light. Precise phase boundaries have been determined by analyzing H-2 NMR line shape. The identification and microstructural characterization of the liquid crystalline phases have been achieved using small-angle X-ray scattering (SAXS). The isotropic liquid Solution phases have been investigated by self-diffusion measurements (PGSE-NMR method). 25R2 does not form liquid crystals and is miscible with water in the whole concentration range; with increasing temperature, the mixtures split into water-rich and a copolymer-rich solutions in equilibrium. 25R4 shows rich phase behavior, passing. with increasing copolymer concentration, from a water-rich solution to a lamellar and copolymer-rich solution. A small hexagonal phase, completely encircled in the stability region of the water-rich solution, is also present. In water-rich solutions, at low temperatures and low copolymer concentrations, the copolymers are dissolved as independent macromolecules. With increasing copolymer concentrations an interconnected network of micelles is formed in which micellar cores of hydrophobic poly(propylene oxide) are interconnected by poly(ethylene oxide) strands. In copolymer-rich solutions water is molecularly dissolved in the copolymer. The factors influencing the self-aggregation of Pluronic R copolymers (PPO-PEO-PPO sequence) are discussed, and their behavior in water is compared to that of Pluronic copolymers (PEO-PPO-PEO sequence). (C) 2004 Elsevier Inc. All rights reserved.
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