Catechol estrogens stimulate insulin secretion in pancreatic β-cells via activation of the transient receptor potential A1 (TRPA1) channel

Estrogen hormones play an important role in controlling glucose homeostasis and pancreatic β-cell function. Despite the significance of estrogen hormones for regulation of glucose metabolism, little is known about the roles of endogenous estrogen metabolites in modulating pancreatic β-cell function. In this study, we evaluated the effects of major natural estrogen metabolites, catechol estrogens, on insulin secretion in pancreatic β-cells. We show that catechol estrogens, hydroxylated at positions C2 and C4 of the steroid A ring, rapidly potentiated glucose-induced insulin secretion via a nongenomic mechanism. 2-Hydroxyestrone, the most abundant endogenous estrogen metabolite, was more efficacious in stimulating insulin secretion than any other tested catechol estrogens. In insulin-secreting cells, catechol estrogens produced rapid activation of calcium influx and elevation in cytosolic free calcium. Catechol estrogens also generated sustained elevations in cytosolic free calcium and evoked inward ion current in HEK293 cells expressing the transient receptor potential A1 (TRPA1) cation channel. Calcium influx and insulin secretion stimulated by estrogen metabolites were dependent on the TRPA1 activity and inhibited with the channel-specific pharmacological antagonists or the siRNA. Our results suggest the role of estrogen metabolism in a direct regulation of TRPA1 activity with potential implications for metabolic diseases

Field distribution and genetic variability of Panicum mosaic virus satellite RNAs in St. Augustine decline

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 48-61).Issued also on microfiche from Lange Micrographics.'St. Augustine decline' is a viral disease associated with St. Augustinegrass, Stenotaphrum secundatum (Walt.) Kuntze, a turfgrass common to the Gulf Coast region of the United States. A survey of 204 plants from two locations in southeast Texas indicates that this disease is a result of an infection with Panicum mosaic virus (genus Panicovirus; family Tombusviridae) (PMV), or in any combination with satellite panicum mosaic virus (SPMV), and/or with its satellite RNAs (satRNAs). In the field, leaf symptoms representative of PMV infections with or without cc-infections by SPMV or satRNAs ranged from a severe bleaching to a mild chlorotic mottle. However, after five months growth in the greenhouse, these symptoms shifted towards a relatively homogeneous chlorotic mottle phenotype, suggesting the influence of environmental conditions. Ribonuclease protection assays (RPAS) indicated a high degree of genetic variability in PMV satRNAs infecting St. Augustinegrass at the College Station (CS) and Corpus Christi (CC) locations. The RPAS grouped satRNAs according to the place of origin, either CS or CC with only 6 exceptions out of 100 satRNAs. Two satRNAs collected in CC were placed in the CS cluster and four collected in CS were placed in CC cluster. Hence, these data shown that different but overlapping population of PMV satRNA can be found in CS and CC

El emprendedorismo y su relación con la informalidad en las microempresas de reciclaje del “sector santa rosa”-San Martín de Porres, 2017

TesisLima NorteEscuela Académico Profesional de AdministraciónAdministración de OperacionesLa investigación “El emprendedorismo y su relación con la informalidad en las microempresas de reciclaje del “sector santa rosa” –San Martín De Porres, 2017”; tuvo como objetivo general determinar la relación del emprendedorismo con la informalidad en las microempresas de reciclaje del “sector santa rosa” – san Martin de Porres, 2017. La población de estudio fue, 30 microempresas de reciclaje ubicadas en el sector “santa rosa”, San Martin de Porres y la muestra fue de 30 microempresas. La técnica de investigación fue la encuesta y un cuestionario de 20 preguntasen la escala de tipo Likert, dirigido hacia los dueños de estas microempresas. La validación del instrumento se realizó mediante juicio de expertos y la Fiabilidad del mismo se calculó a través del coeficiente Alfa de Crombach. Recolectados los datos se procesaron mediante el SPSS V. 20. Teniendo como resultado que la relación del emprendedorismo con la informalidad es significativa, y se concluye que para que la empresa aumente su rentabilidad es importante realizar un emprendimiento de acorde a los parámetros establecidos por el marco legal y normativo

The Different Faces of the Pancreatic Islet

Type 1 diabetes (T1D) patients who receive pancreatic islet transplant experience significant improvement in their quality-of-life. This comes primarily through improved control of blood sugar levels, restored awareness of hypoglycemia, and prevention of serious and potentially life-threatening diabetes-associated complications, such as kidney failure, heart and vascular disease, stroke, nerve damage, and blindness. Therefore, beta cell replacement through transplantation of isolated islets is an important option in the treatment of T1D. However, lasting success of this promising therapy depends on durable survival and efficacy of the transplanted islets, which are directly influenced by the islet isolation procedures. Thus, isolating pancreatic islets with consistent and reliable quality is critical in the clinical application of islet transplantation.Quality of isolated islets is important in pre-clinical studies as well, as efforts to advance and improve clinical outcomes of islet transplant therapy have relied heavily on animal models ranging from rodents, to pigs, to nonhuman primates. As a result, pancreatic islets have been isolated from these and other species and used in a variety of in vitro or in vivo applications for this and other research purposes. Protocols for islet isolation have been somewhat similar across species, especially, in mammals. However, given the increasing evidence about the distinct structural and functional features of human and mouse islets, using similar methods of islet isolation may contribute to inconsistencies in the islet quality, immunogenicity, and experimental outcomes. This may also contribute to the discrepancies commonly observed between pre-clinical findings and clinical outcomes. Therefore, it is prudent to consider the particular features of pancreatic islets from different species when optimizing islet isolation protocols.In this chapter, we explore the structural and functional features of pancreatic islets from mice, pigs, nonhuman primates, and humans because of their prevalent use in nonclinical, preclinical, and clinical applications

Extracellular ATP is a positive autocrine signal for insulin release in the human pancreatic beta‐cell

ATP has been proposed to be co‐released with insulin to act as an autocrine signal in insulin secretion of pancreatic islets, but published data are inconclusive. Because human islet biology is unique, we measured both dynamic insulin release and cytoplasmic free Ca2+ concentration, [Ca2+]i, to investigate the functional role of purinergic receptors in human β cells. Activation of ionotropic (P2X) and metabotropic (P2Y) purinergic receptors increased insulin secretion. ATP elicited [Ca2+]i responses in β cells that were dependent on extracellular Ca2+, suggesting P2X receptor activation. Human β cells were immunoreactive for P2X2 and P2X3 receptors. To test the role of endogenously released ATP on glucose‐induced insulin release, we investigated the effect of P2 receptor antagonists. Suramin (P2 antagonist), isoPPADS and oxidized ATP (P2X antagonists) reduced insulin release by 40%, 30%, and 65%, respectively. Reactive blue 2 (P2Y antagonist) had no effect. Glucose‐induced insulin release was decreased by apyrase, an enzyme that degrades extracellular ATP. We conclude that ATP is a positive autocrine signal for insulin secretion in human pancreatic β‐cells. Autocrine signaling may thus be a prerequisite for a functional endocrine pancreas, allowing for adequate hormone release under physiological conditions where blood glucose concentration is only modestly changed. Supported by JDRF and DRI