排序方式: 共有27条查询结果,搜索用时 15 毫秒
21.
Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels 总被引:16,自引:0,他引:16
P Rorsman P O Berggren K Bokvist H Ericson H M?hler C G Ostenson P A Smith 《Nature》1989,341(6239):233-236
The endocrine part of the pancreas plays a central role in blood-glucose regulation. It is well established that an elevation of glucose concentration reduces secretion of the hyperglycaemia-associated hormone glucagon from pancreatic alpha 2 cells. The mechanisms involved, however, remain unknown. Electrophysiological studies have demonstrated that alpha 2 cells generate Ca2+-dependent action potentials. The frequency of these action potentials, which increases under conditions that stimulate glucagon release, is not affected by glucose or insulin. The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is present in the endocrine part of the pancreas at concentrations comparable to those encountered in the central nervous system, and co-localizes with insulin in pancreatic beta cells. We now describe a mechanism whereby GABA, co-secreted with insulin from beta cells, may mediate part of the inhibitory action of glucose on glucagon secretion by activating GABAA-receptor Cl- channels in alpha 2 cells. These observations provide a model for feedback regulation of glucagon release, which may be of significance for the understanding of the hypersecretion of glucagon frequently associated with diabetes. 相似文献
22.
23.
Inositol pyrophosphates: structure, enzymology and function 总被引:2,自引:0,他引:2
Christopher John Barker Christopher Illies Gian Carlo Gaboardi Per-Olof Berggren 《Cellular and molecular life sciences : CMLS》2009,66(24):3851-3871
The stereochemistry of the inositol backbone provides a platform on which to generate a vast array of distinct molecular motifs that are used to convey information both in signal transduction and many other critical areas of cell biology. Diphosphoinositol phosphates, or inositol pyrophosphates, are the most recently characterized members of the inositide family. They represent a new frontier with both novel targets within the cell and novel modes of action. This includes the proposed pyrophosphorylation of a unique subset of proteins. We review recent insights into the structures of these molecules and the properties of the enzymes which regulate their concentration. These enzymes also act independently of their catalytic activity via protein–protein interactions. This unique combination of enzymes and products has an important role in diverse cellular processes including vesicle trafficking, endo- and exocytosis, apoptosis, telomere length regulation, chromatin hyperrecombination, the response to osmotic stress, and elements of nucleolar function. 相似文献
24.
Dekki N Refai E Holmberg R Köhler M Jörnvall H Berggren PO Juntti-Berggren L 《Cellular and molecular life sciences : CMLS》2012,69(10):1733-1743
Transthyretin (TTR) is a functional protein in the pancreatic β-cell. It promotes insulin release and protects against β-cell
death. We now demonstrate by ligand blotting, adsorption to specific magnetic beads, and surface plasmon resonance that TTR
binds to glucose-regulated proteins (Grps)78, 94, and 170, which are members of the endoplasmic reticulum chaperone family,
but Grps78 and 94 have also been found at the plasma membrane. The effect of TTR on changes in cytoplasmic free Ca2+ concentration ([Ca2+]i) was abolished if the cells were treated with either dynasore, a specific inhibitor of dynamin GTPase that blocks clathrin-mediated
endocytosis, or an antibody against Grp78, that prevents TTR from binding to Grp78. The conclusion is that TTR binds to Grp78
at the plasma membrane, is internalized into the β-cell via a clathrin-dependent pathway, and that this internalization is
necessary for the effects of TTR on β-cell function. 相似文献
25.
A Vazquez-Torres J Jones-Carson A J B?umler S Falkow R Valdivia W Brown M Le R Berggren W T Parks F C Fang 《Nature》1999,401(6755):804-808
Specialized epithelia known as M cells overlying the lymphoid follicles of Peyer's patches are important in the mucosal immune system, but also provide a portal of entry for pathogens such as Salmonella typhimurium, Mycobacterium bovis, Shigella flexneri, Yersinia enterocolitica and reoviruses. Penetration of intestinal M cells and epithelial cells by Salmonella typhimurium requires the invasion genes of Salmonella Pathogenicity Island 1 (SPI1). SPI1-deficient S. typhimurium strains gain access to the spleen following oral administration and cause lethal infection in mice without invading M cells or localizing in Peyer's patches, which indicates that Salmonella uses an alternative strategy to disseminate from the gastrointestinal tract. Here we report that Salmonella is transported from the gastrointestinal tract to the bloodstream by CD18-expressing phagocytes, and that CD18-deficient mice are resistant to dissemination of Salmonella to the liver and spleen after oral administration. This CD18-dependent pathway of extraintestinal dissemination may be important for the development of systemic immunity to gastrointestinal pathogens, because oral challenge with SPI1-deficient S. typhimurium elicits a specific systemic IgG humoral immune response, despite an inability to stimulate production of specific mucosal IgA. 相似文献
26.
Irina I. Zaitseva Monica Hultcrantz Vladimir Sharoyko Malin Flodström-Tullberg Sergei V. Zaitsev Per-Olof Berggren 《Cellular and molecular life sciences : CMLS》2009,66(23):3787-3795
Pancreatic beta cell damage caused by pro-inflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) is a key event in the pathogenesis of type 1 diabetes. The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNγ-induced signaling and prevents diabetes in the non-obese diabetic mouse. Here, we investigated if SOCS-1 overexpression in primary beta cells provides protection from cytokine-induced islet cell dysfunction and death. We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1β, IFNγ, TNFα. However, it decreases the activation of caspase-3, -8 and -9, and thereby, promotes a robust protection from cytokine-induced beta cell death. Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNγ in beta cells. In summary, we show that interference with IFNγ signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death. 相似文献
27.
The ultrastructural morphology of the clonal insulin-producing cell line, RINm5F, was investigated. Virus-like particles, probably C type viruses, were identified both intra- and extracellularly. Because these particles could not be found in the original transplantable tumor, it is probable that viruses were induced at some later stage in the development of the RINm5F cell line. All investigators using the RINm5F cells should be aware of the fact that these cells may contain one or several types of viruses, and of the possibility that these particles may interfere with a variety of cellular functions. 相似文献