| 1. |
- Meidute, Sandra, et al.
(författare)
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Palmitate-induced beta-cell dysfunction is associated with excessive NO pro-duction and is reversed by thiazolidinedione-mediated inhibition of GPR40 transduction mechanisms
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). ; 3:5
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Background: Type 2 diabetes often displays hyperlipidemia. We examined palmitate effects on pancreatic islet function in relation to FFA receptor GPR40, NO generation, insulin release, and the PPARgama agonistic thiazolidinedione, rosiglitazone. Principal findings: Rosiglitazone suppressed acute palmitate-stimulated GPR40-transduced PI hydrolysis in HEK293 cells and insulin release from MIN6c cells and mouse islets. Culturing islets 24 h with palmitate at 5 mmol/l glucose induced beta-cell iNOS expression as revealed by confocal microscopy and in-creased the activities of ncNOS and iNOS associated with suppression of glucose-stimulated insulin response. Rosiglitazone reversed these effects. The expression of iNOS after high-glucose culturing was unaffected by rosiglitazone. Downregulation of GPR40 by antisense treatment abrogated GPR40 expression and suppressed palmitate-induced iNOS activity and insulin release. Conclusion: We conclude that, in addition to mediating acute FFA-stimulated insulin release, GPR40 is an important regulator of iNOS expression and dysfunctional insulin release during long-term exposure to FFA. The adverse effects of palmitate were counteracted by rosiglitazone at GPR40, suggesting that thiazolidinediones are beneficial for beta-cell function in hyperlipidemic type 2 diabetes.
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| 2. |
- Minnhagen, Petter, 1946-, et al.
(författare)
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The blind watchmaker network : Scale-freeness and evolution
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:2, s. e1690-1-e1690-5
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- It is suggested that the degree distribution for networks of the cell-metabolism for simple organisms reflects an ubiquitous randomness. This implies that natural selection has exerted no or very little pressure on the network degree distribution during evolution. The corresponding random network, here termed the blind watchmaker network has a power-law degree distribution with an exponent gamma >= 2. It is random with respect to a complete set of network states characterized by a description of which links are attached to a node as well as a time-ordering of these links. No a priory assumption of any growth mechanism or evolution process is made. It is found that the degree distribution of the blind watchmaker network agrees very precisely with that of the metabolic networks. This implies that the evolutionary pathway of the cell-metabolism, when projected onto a metabolic network representation, has remained statistically random with respect to a complete set of network states. This suggests that even a biological system, which due to natural selection has developed an enormous specificity like the cellular metabolism, nevertheless can, at the same time, display well defined characteristics emanating from the ubiquitous inherent random element of Darwinian evolution. The fact that also completely random networks may have scale-free node distributions gives a new perspective on the origin of scale-free networks in general.
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