Modulation of β-Cell Ouabain-Sensitive 86Rb+ Influx (Na+/K+ Pump) by D-Glucose, Glibenclamide or Diazoxide

The activity of the β-cell Na+/K+ pump was studied by using ouabain-sensitive (lmM ouabain) 86Rb+ influx in β-cell-rich islets of Umeå-ob/ob mice as an indicator of the pump function. The present results show that the stimulatory effect of glucose on ouabain-sensitive 86Rb+ influx reached its approximate maximum at 5mM glucose. Pre-treatment of the islets with 20mM glucose for 60 min strongly reduced the glucose-induced stimulation of the Na+/K+ pump. Pre-treatment (60 or 180 min) of islets at 0mM glucose, on the other hand, did not affect the magnitude of the glucose-induced stimulation of 86Rb+ influx dunng the subsequent 5-min incubation. Glibenclamide stimulated the ouabain-sensitive 86Rb+ uptake in the same manner as glucose. The stimulatory effect, showed its apparent maximum at 0.5μM. Pre-treatment (60 min) of islets with 1μM glibenclamide did not reduce the subsequent stimulation of the ouabain-sensitive 86Rb+ influx. The stimulatory effect of glibenclamide and D-glucose were not .additive, suggesting that they may have the same mechanism of action. No direct effect of glibenclamide (0.01-1μM) was observed on the Na+/K+ ATPase activity in homogenates of islets. Diazoxide (0.4mM) inhibited the Na+/K+ pump. This effect was sustained even after 60 min of pre-treatment of islets with 0.4mM diazoxide. The stimulatory effect of glibenclamide and D-glucose were abolished by diazoxide. It is concluded that nutrient as well as non-nutrient insulin secretagogues activate the Na+/K+ pump, probably as part of the membrane repolarisation process

D-glucose Stimulates the Na+/K+ Pump in Mouse Pancreatic Islet Cells

To determine the effect of D-glucose on the β-cell Na+/K+ pump, 86Rb+ influx was studied in isolated, -cell-rich islets of Umeå-ob/ob mice in the absence or presence of lmM ouabain. D-glucose (20 mM) stimulated the ouabain-sensitive portion of 86Rb+ influx by 65%, whereas the ouabain-resistant portion was inhibited by 48%. The Na+/K+ ATPase activity in homogenates of islets of Umeå-ob/ob mice or normal mice was determined to search for direct effects of D-glucose. Thus, ouabain-sensitive ATP hydrolysis in islet homogenates was measured in the presence of different D-glucose concentrations. No effect of D-glucose (3–20 mM) was observed in either ob/ob or normal islets at the optimal Na+/K+ ratio for the enzyme (135 mM Na+ and 20 mM K+). Neither D-glucose (3–20 mM) nor L-glucose or 3-O-methyl-D-glucose (20 mM) affected the enzyme activity at a high Na+/K+ ratio (175 mM Na+ and 0.7mM K+). Diphenylhydantoin (150 μM) decreased the enzyme activity at optimal Na+/K+ ratio, whereas 50 μM of the drug had no effect. The results suggest that D-glucose induces a net stimulation the Na+/K+ pump of β-cells in intact islets and that D-glucose does not exert any direct effect on the Na+/K+ ATPase activity

Blombok

Blombok handlar om krukväxter och människor. Hur vi mår bra av att ha levande växter i vår innemiljö. Krukväxter kan betyda mycket, något att vårda, ett minne och en bättre inomhusluft

Себестоимость продукции предприятия: управление и направления снижения (на примере ОАО «Мозырский машиностроительный завод»)

De arbetsmarknadspolitiska programmens insatser riktas åt olika håll. Detta beror på att Arbetsförmedlingen och Försäkringskassan gör antaganden om olika sociala kategoriers egenskaper, kvalifikationer och behov. Den här studien visar att arbetsmarknadspolitiska program skapar och vidmakthåller synen på att det finns “starkt” och “svagt” på arbetsmarknaden, vilket antas bero på personliga egenskaper och kvalifikationer. Studien analyserar hur sådana antaganden bidrar till att upprätthålla en utestängningsprocess på arbetsmarknaden. Med utgångspunkt i kritisk diskursanalys har språket i arbetsmarknadspolitiska program granskats och problematiserats för att identifiera vilka antaganden som påverkar deras insatser. Studien är baserad på Carol Bacchis metod för policyanalys: “What’s The Problem Represented To Be?” Inga tidigare studier har påträffats som granskar hur språket i svenska arbetsmarknadspolitiska program synliggör normer och antaganden. Inte heller har några tidigare studier problematiserat att normer och antaganden styr och formar programmens insatser. Denna studie bidrar därför med viktig kunskap till forskningsfältet liksom för Arbetsförmedlingen och Försäkringskassan.   

Chemical Imaging of Evolving Amyloid Plaque Pathology and Associated Aβ Peptide Aggregation in a Transgenic Mouse Model of Alzheimer's Disease

One of the major hallmarks of Alzheimer's disease (AD) pathology is the formation of extracellular amyloid β (Aβ) plaques. While Aβ has been suggested to be critical in inducing and, potentially, driving the disease, the molecular basis of AD pathogenesis is still under debate. Extracellular Aβ plaque pathology manifests itself upon aggregation of distinct Aβ peptides, resulting in morphologically different plaque morphotypes, including mainly diffuse and cored senile plaques. As plaque pathology precipitates long before any clinical symptoms occur, targeting the Aβ aggregation processes provides a promising target for early interventions. However, the chain of events of when, where and what Aβ species aggregate and form plaques remains unclear. The aim of the current study was to investigate the potential of MALDI-IMS as a tool to study the evolving pathology in transgenic mouse models for AD. To that end, we used an emerging, chemical imaging modality - MALDI imaging mass spectrometry - that allows for delineating Aβ aggregation with specificity at the single plaque level. We identified that plaque formation occurs first in cortical regions and that these younger plaques contain higher levels of 42 amino acid-long Aβ (Aβ1-42). Plaque maturation was found to be characterized by a relative increase in deposition of Aβ1-40, which was associated with the appearance of a cored morphology of the plaques. Finally, other C-terminally truncated Aβ species (Aβ1-38 and Aβ1-39) exhibited a similar aggregation pattern as Aβ1-40, suggesting that these species have similar aggregation characteristics. These results suggest that initial plaque formation is seeded by Aβ1-42; a process that is followed by plaque maturation upon deposition of Aβ1-40 as well as deposition by other C-terminally modified Aβ species

In vitro stimulation of insulin release by non-metabolizable, transport-specific amino acids

The insulin-releasing ability and uptake characteristics of non-metabolizable, transport-specific amino acids were studied in an in vitro system, using microdissected pancreatic islets with more than 90% [beta]-cells.Among the four stereoisomers of 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid (BCH), only the b(-) form stimulated insulin release. This isomer is known as a specific substrate for transport system in other cells. It was rapidly taken up by the islet cells and stimulated insulin release both in the presence and in the absence of glucose.4-Amino-1-guanylpiperidine-4-carboxylic acid (GPA), a substrate for cationic transport systems, stimulated insulin release in the presence but not in the absence of glucose. In this respect GPA is similar to arginine. Like arginine, GPA also accumulated in the islet cells to yield distribution ratios well above unity.The results are consonant with the previous hypothesis that amino acids stimulate insulin release by binding to specific transport molecules.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33579/1/0000082.pd