| 1. |
- Schumann, DM, et al.
(författare)
-
The Fas pathway is involved in pancreatic beta cell secretory function
- 2007
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 104:8, s. 2861-2866
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic β cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in β cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates β cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a β cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient β cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased β cell mass. Up-regulation of FLIP enhanced NF-κB activity via NF-κB-inducing kinase and RelB. This led to increased PDX-1 and insulin production independent of changes in cell turnover. The results support a previously undescribed role for the Fas pathway in regulating insulin production and release.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Konrad, D, et al.
(författare)
-
Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.
- 2005
-
Ingår i: Am J Physiol Heart Circ Physiol. - : American Physiological Society. - 0363-6135 .- 1522-1539. ; 289:4
-
Tidskriftsartikel (refereegranskat)abstract
- The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.
|
|
| 5. |
- Konrad-Schmolke, Matthias, 1970, et al.
(författare)
-
Combined thermodynamic and rare earth element modelling of garnet growth during subduction: Examples from ultrahigh-pressure eclogite of the Western Gneiss Region, Norway
- 2008
-
Ingår i: Earth and Planetary Science Letters. - 0012-821X. ; 272:1-2, s. 488-498
-
Tidskriftsartikel (refereegranskat)abstract
- Major and trace element zonation patterns were determined in ultrahigh-pressure eclogite garnets from the Western Gneiss Region (Norway). All investigated garnets show Multiple growth zones and preserve complex growth zonation patterns with respect to both major and rare earth elements (REE). Due to chemical differences of the host rocks two types of major element compositional zonation patterns occur: (1) abrupt, step-like compositional changes corresponding with the growth zones and (2) compositionally homogeneous interiors, independent of growth zones, followed by abrupt chemical changes towards the rims. Despite differences in major element zonation, the REE patterns are almost identical in all garnets and can be divided into four distinct zones with characteristic patterns. In order to interpret the major and trace element distribution and zoning patterns in terms of the subduction history of the rocks, we combined thermodynamic forward models for appropriate bulk rock compositions to yield molar proportions and major element compositions of stable phases along the inferred pressure-temperature path with a mass balance distribution of REEs among the calculated stable phases during high pressure metamorphism. Our thermodynamic forward models reproduce the complex major element zonation patterns and growth zones in the natural garnets, with garnet growth predicted during four different reaction stages: (1) chlorite breakdown, (2) epidote breakdown, (3) amphibole breakdown and (4) reduction in molar clinopyroxene at ultrahigh-pressure conditions. Mass-balance of the rare earth element distribution among the modelled stable phases yielded characteristic zonation patterns in garnet that closely resemble those in the natural samples. Garnet growth and trace element incorporation Occurred in near thermodynamic equilibrium with matrix phases during subduction. The rare earth element patterns in garnet exhibit distinct enrichment zones that fingerprint the minerals involved in the garnet-forming reactions as well as local peaks that can be explained by fractionation effects and changes in the mineral assemblage. (C) 2008 Elsevier B.V. All rights reserved.
|
|
| 6. |
|
|
| 7. |
|
|
