scholarly journals Normal and defective pathways in biogenesis and maintenance of the insulin storage pool

2021 ◽  
Vol 131 (2) ◽  
Author(s):  
Ming Liu ◽  
Yumeng Huang ◽  
Xiaoxi Xu ◽  
Xin Li ◽  
Maroof Alam ◽  
...  
Keyword(s):  
Storage Pool ◽  
Insulin Storage

Evaluation of platelet dense granules for determining storage pool deficiencies by HVEM image and quantitative analysis

1996 ◽  
Vol 54 ◽  
pp. 770-771
Author(s):  
W.T. Gunning ◽  
J.N. Turner ◽  
K. Buttle ◽  
E.P. Calomeni ◽  
N.A. Lachant ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Platelet Function ◽  
Electron Microscopic ◽  
Von Willebrand's Disease ◽  
Dense Granules ◽  
Storage Pool ◽  
Prolonged Bleeding ◽  
Microscopic Evaluation ◽  
Storage Pools ◽  
Electron Lucent

There are a variety of conditions which have been associated with prolonged bleeding times. If other etiologies including von Willebrand's disease have been ruled out, a platelet function disorder must be considered. The best, if not only, technique to make this diagnosis is the electron microscopic evaluation of whole air dried platelets. Bull first described the presence of dense granules in whole platelets in 1968 and the technique has been utilized extensively The electron dense or delta granules are easily distinguished from the larger more numerous alpha granules which are electron lucent. The significance of the dense granules is that they are known to be “storage pools” of serotonin, calcium, adenosine di- and triphosphate, and pyrophosphate. Prolonged bleeding times may be directly related to an insufficiency of these substances. The diagnosis of a storage pool deficiency is made when either the storage content of the dense granules is abnormal or their number is diminished. We observe normal platelets to have 4-6 dense granules, which agrees with the literature.

Rekombinanter Faktor VIIa bei Patienten mit Plättchenfunktionsstörungen oder Thrombozytopenien

2007 ◽  
Vol 27 (04) ◽  
pp. 251-262 ◽  
Author(s):  
R. E. Scharf ◽  
R. B. Zotz
Keyword(s):  
Storage Pool ◽  
Rekombinanter Faktor Viia

ZusammenfassungRekombinanter Faktor VIIa (rFVIIa) wird über die zugelassenen Indikationen hinaus zunehmend zur Behandlung lebensbedrohlicher Blutungsereignissen bei Versagen der jeweiligen Standardtherapien eingesetzt. Kasuistiken und Fallserien dokumentieren die Wirksamkeit und Sicherheit von rFVIIa zur Blutstillung bei Patienten mit Thrombozytopathien und Thrombozytopenien verschiedener Ursache. Eine Zulassung zur Anwendung von rFVIIa liegt bei Patienten mit Thrombasthenie Glanzmann im Falle eines Refraktärzustandes auf die Transfusion von Thrombozytenkonzentraten vor. rFVIIa-Bolusapplikationen mit Dosierungen zwischen 80 und 120 μg/kg Körpergewicht alle 1,5 bis 3 Stunden werden auch bei Bernard-Soulier-Syndrom, Plättchen- Storage-Pool-Defekten und verschiedenen erworbenen Thrombozytopathien erfolgreich eingesetzt. Bei Thrombasthenie Glanzmann sind zur Gewährleistung einer effektiven Hämostase mindestens drei Bolusgaben notwendig. Bei Thrombozytopenie hat sich bei annähernd der Hälfte der Patienten ein einzelner rFVIIa-Bolus zur Beherrschung sonst unstillbarer Blutungen als ausreichend erwiesen. Dabei kann eine Blutstillung unter rFVIIa auch bei Thrombozytenwerten unter 20 000/μl erreicht werden, wenngleich bei höheren Thrombozytenkonzentrationen eine bessere Wirksamkeit erzielbar ist.

Correlation Between Noradrenaline Fluxes, Metabolism and Compartmentalisation in Human Platelets

1982 ◽  
Vol 48 (01) ◽  
pp. 062-066 ◽  
Author(s):  
Chantal Legrand ◽  
Véronique Dubernard ◽  
Philippe Meyer
Keyword(s):  
Noradrenaline Release ◽  
Human Platelets ◽  
Release Of Noradrenaline ◽  
Storage Pool ◽  
Platelet Storage ◽  
Efflux Of Noradrenaline ◽  
Preferential Localization

Summary(3H) noradrenaline was taken up by human platelets and partially converted into sulfoconjugated noradrenaline. This uptake was inhibited by drugs which have been previously shown to impair the uptake of 5-HT (ouabain, chlorimipramine) or the storage of 5-HT (tyramine, reserpine) by platelets. In addition, tyramine and reserpine stimulated the formation of sulfoconjugated noradrenaline. The efflux of noradrenaline from platelets was measured in parallel and was found to be directly related to the proportion of non metabolized to metabolized noradrenaline in the cells. Unlike tyramine, which induced a similar release of noradrenaline and 5-HT, reserpine was less effective at inducing noradrenaline release than 5-HT release. This study indicates a preferential localization of noradrenaline in the granular pool of human platelets with the existence of an extragranular sulfoconjugated pool which is increased when the granular storage of noradrenaline is impaired. Studies of noradrenaline fluxes and metabolism may be useful in the understanding of both acquired and inherited platelet storage pool defects.

Enhanced Increases in Cytosolic Ca2+ in ADP-Stimulated Platelets from Patients with Delta-Storage Pool Deficiency – A Possible Indicator of Interactions between Granule-Bound ADP and the Membrane ADP Receptor

1997 ◽  
Vol 77 (02) ◽  
pp. 376-382 ◽  
Author(s):  
Bruce Lages ◽  
Harvey J Weiss
Keyword(s):  
Platelet Rich Plasma ◽  
Limited Range ◽  
Dense Granule ◽  
Receptor Desensitization ◽  
Fura 2 ◽  
Storage Pool ◽  
Low Levels ◽  
The Right

SummaryThe possible involvement of secreted platelet substances in agonist- induced [Ca2+]i increases was investigated by comparing these increases in aspirin-treated, fura-2-loaded normal platelets and platelets from patients with storage pool deficiencies (SPD). In the presence and absence of extracellular calcium, the [Ca2+]i response induced by 10 µM ADP, but not those induced by 0.1 unit/ml thrombin, 3.3 µM U46619, or 20 µM serotonin, was significantly greater in SPD platelets than in normal platelets, and was increased to the greatest extent in SPD patients with Hermansky-Pudlak syndrome (HPS), in whom the dense granule deficiencies are the most severe. Pre-incubation of SPD-HPS and normal platelets with 0.005-5 µM ADP produced a dose-dependent inhibition of the [Ca2+]i response induced by 10 µ M ADP, but did not alter the [Ca2+]i increases induced by thrombin or U46619. Within a limited range of ADP concentrations, the dose-inhibition curve of the [Ca2+]i response to 10 µM ADP was significantly shifted to the right in SPD-HPS platelets, indicating that pre-incubation with greater amounts of ADP were required to achieve the same extent of inhibition as in normal platelets. These results are consistent with a hypothesis that the smaller ADP-induced [Ca2+]i increases seen in normal platelets may result from prior interactions of dense granule ADP, released via leakage or low levels of activation, with membrane ADP receptors, causing receptor desensitization. Addition of apyrase to platelet-rich plasma prior to fura-2 loading increased the ADP-induced [Ca2+]i response in both normal and SPD-HPS platelets, suggesting that some release of ADP derived from both dense granule and non-granular sources occurs during in vitro fura-2 loading and platelet washing procedures. However, this [Ca2+]i response was also greater in SPD-HPS platelets when blood was collected with minimal manipulation directly into anticoagulant containing apyrase, raising the possibility that release of dense granule ADP resulting in receptor desensitization may also occur in vivo. Thus, in addition to enhancing platelet activation, dense granule ADP could also act to limit the ADP-mediated reactivity of platelets exposed in vivo to low levels of stimulation.

Detection of an Acquired Platelet Storage Pool Disease in Three Patients with a Myeloproliferative Disorder

1979 ◽  
Vol 42 (02) ◽  
pp. 794-796 ◽  
Author(s):  
Francine Rendu ◽  
Marilyne Lebret ◽  
Alan Nurden ◽  
Jacques P Caen
Keyword(s):  
Myeloproliferative Disorder ◽  
Storage Pool ◽  
Platelet Storage ◽  
Storage Pool Disease

Fast Insulin Secretion Blunted by Impaired Insulin Storage of Islet ß Cells in Mice

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2468-PUB
Author(s):  
YINAN ZHAO ◽  
TIAN ZHAO ◽  
AILUN ZONG ◽  
YINGSHENG ZHOU
Keyword(s):  
Insulin Secretion ◽  
Impaired Insulin ◽  
Insulin Storage ◽  
Fast Insulin

scholarly journals Nuclear condensates of p300 formed though the structured catalytic core can act as a storage pool of p300 with reduced HAT activity

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi Zhang ◽  
Kyle Brown ◽  
Yucong Yu ◽  
Ziad Ibrahim ◽  
Mohamad Zandian ◽  
...  
Keyword(s):  
Phase Separation ◽  
Cell Nucleus ◽  
Active Site ◽  
Histone Acetyltransferase ◽  
Histone H3 ◽  
Catalytic Core ◽  
Cellular Processes ◽  
Storage Pool ◽  
Core Components ◽  
Acetyltransferase P300

AbstractThe transcriptional co-activator and acetyltransferase p300 is required for fundamental cellular processes, including differentiation and growth. Here, we report that p300 forms phase separated condensates in the cell nucleus. The phase separation ability of p300 is regulated by autoacetylation and relies on its catalytic core components, including the histone acetyltransferase (HAT) domain, the autoinhibition loop, and bromodomain. p300 condensates sequester chromatin components, such as histone H3 tail and DNA, and are amplified through binding of p300 to the nucleosome. The catalytic HAT activity of p300 is decreased due to occlusion of the active site in the phase separated droplets, a large portion of which co-localizes with chromatin regions enriched in H3K27me3. Our findings suggest a model in which p300 condensates can act as a storage pool of the protein with reduced HAT activity, allowing p300 to be compartmentalized and concentrated at poised or repressed chromatin regions.

scholarly journals Inside the Insulin Secretory Granule

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 515
Author(s):  
Mark Germanos ◽  
Andy Gao ◽  
Matthew Taper ◽  
Belinda Yau ◽  
Melkam A. Kebede
Keyword(s):  
Secretory Granules ◽  
Β Cells ◽  
Β Cell ◽  
Proinsulin Processing ◽  
Membrane Bound ◽  
Golgi Network ◽  
Insulin Secretory Granule ◽  
Insulin Storage ◽  
Cellular Stimulation

The pancreatic β-cell is purpose-built for the production and secretion of insulin, the only hormone that can remove glucose from the bloodstream. Insulin is kept inside miniature membrane-bound storage compartments known as secretory granules (SGs), and these specialized organelles can readily fuse with the plasma membrane upon cellular stimulation to release insulin. Insulin is synthesized in the endoplasmic reticulum (ER) as a biologically inactive precursor, proinsulin, along with several other proteins that will also become members of the insulin SG. Their coordinated synthesis enables synchronized transit through the ER and Golgi apparatus for congregation at the trans-Golgi network, the initiating site of SG biogenesis. Here, proinsulin and its constituents enter the SG where conditions are optimized for proinsulin processing into insulin and subsequent insulin storage. A healthy β-cell is continually generating SGs to supply insulin in vast excess to what is secreted. Conversely, in type 2 diabetes (T2D), the inability of failing β-cells to secrete may be due to the limited biosynthesis of new insulin. Factors that drive the formation and maturation of SGs and thus the production of insulin are therefore critical for systemic glucose control. Here, we detail the formative hours of the insulin SG from the luminal perspective. We do this by mapping the journey of individual members of the SG as they contribute to its genesis.

scholarly journals A Platelet Acquired Storage Pool Disorder Associated with Tamoxifen Therapy

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Lalitha Nayak ◽  
Alvin H. Schmaier
Keyword(s):  
Breast Cancer ◽  
Platelet Function ◽  
Tooth Extraction ◽  
Function Analysis ◽  
Tamoxifen Therapy ◽  
Storage Pool ◽  
Prolonged Bleeding ◽  
Platelet Storage

The antiestrogenic drug tamoxifen, used in patients with breast cancer, is associated with an increase in arterial and venous thrombotic events, the mechanism of which is not clearly understood. We report a case of a lady who presented with new bruising and prolonged bleeding following a tooth extraction 4–6 weeks after starting tamoxifen. Investigations were consistent with an acquired platelet storage pool disorder. Repeat platelet function analysis was normal, performed 3 months after discontinuation of tamoxifen. We present a previously clinically unreported effect of tamoxifen on platelet function.

scholarly journals Osmotically inactive sodium and potassium storage: lessons learned from the Edelman and Boling data

2016 ◽  
Vol 311 (3) ◽  
pp. F539-F547 ◽  
Author(s):  
Minhtri K. Nguyen ◽  
Dai-Scott Nguyen ◽  
Minh-Kevin Nguyen
Keyword(s):  
Linear Regression ◽  
Measurement Errors ◽  
Linear Regression Analysis ◽  
Sodium Concentration ◽  
Lessons Learned ◽  
Dynamic Changes ◽  
Data Set ◽  
Storage Pool ◽  
Total Body ◽  
Sodium And Potassium

Because changes in the plasma water sodium concentration ([Na+]pw) are clinically due to changes in the mass balance of Na+, K+, and H2O, the analysis and treatment of the dysnatremias are dependent on the validity of the Edelman equation in defining the quantitative interrelationship between the [Na+]pw and the total exchangeable sodium (Nae), total exchangeable potassium (Ke), and total body water (TBW) (Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. J Clin Invest 37: 1236–1256, 1958): [Na+]pw = 1.11(Nae + Ke)/TBW − 25.6. The interrelationship between [Na+]pw and Nae, Ke, and TBW in the Edelman equation is empirically determined by accounting for measurement errors in all of these variables. In contrast, linear regression analysis of the same data set using [Na+]pw as the dependent variable yields the following equation: [Na+]pw = 0.93(Nae + Ke)/TBW + 1.37. Moreover, based on the study by Boling et al. (Boling EA, Lipkind JB. 18: 943–949, 1963), the [Na+]pw is related to the Nae, Ke, and TBW by the following linear regression equation: [Na+]pw = 0.487(Nae + Ke)/TBW + 71.54. The disparities between the slope and y-intercept of these three equations are unknown. In this mathematical analysis, we demonstrate that the disparities between the slope and y-intercept in these three equations can be explained by how the osmotically inactive Na+ and K+ storage pool is quantitatively accounted for. Our analysis also indicates that the osmotically inactive Na+ and K+ storage pool is dynamically regulated and that changes in the [Na+]pw can be predicted based on changes in the Nae, Ke, and TBW despite dynamic changes in the osmotically inactive Na+ and K+ storage pool.

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