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- Gruber, Kenneth A, et al.
(författare)
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Neuropeptide Y and gamma-melanocyte stimulating hormone (gamma-MSH) share a common pressor mechanism of action
- 2009
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 35:3, s. 312-324
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Tidskriftsartikel (refereegranskat)abstract
- Central circuits known to regulate food intake and energy expenditure also affect central cardiovascular regulation. For example, both the melanocortin and neuropeptide Y (NPY) peptide families, known to regulate food intake, also produce central hypertensive effects. Members of both families share a similar C-terminal amino acid residue sequence, RF(Y) amide, a sequence distinct from that required for melanocortin receptor binding. A recently delineated family of RFamide receptors recognizes both of these C-terminal motifs. We now present evidence that an antagonist with Y1 and RFamide receptor activity, BIBO3304, will attenuate the central cardiovascular effects of both gamma-melanocyte stimulating hormone (gamma-MSH) and NPY. The use of synthetic melanocortin and NPY peptide analogs excluded an interaction with melanocortin or Y family receptors. We suggest that the anatomical convergence of NPY and melanocortin neurons on cardiovascular control centers may have pathophysiological implications through a common or similar RFamide receptor(s), much as they converge on other nuclei to coordinately control energy homeostasis.
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- Movérare-Skrtic, Sofia, et al.
(författare)
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Peripheral blood leukocyte distribution and body mass index are associated with the methylation pattern of the androgen receptor promoter.
- 2009
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 0969-711X .- 1355-008X .- 1559-0100. ; 35:2, s. 204-210
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Tidskriftsartikel (refereegranskat)abstract
- Methylation of CpG sites in the promoter region can affect gene transcription. DNA derived from peripheral blood leukocytes (PBL) from the well-characterized clinical cohorts might be useful to study the influence of environmental factors on DNA methylation. However, these studies could be confounded by the heterogeneous nature of PBL. The aims of this study were to determine the impact of PBL distribution on methylation status of the androgen receptor (AR) promoter, and determine the associations between PBL distribution-adjusted methylation status of the AR promoter and AR-related phenotypes. PBL differential count analyses were performed at the time of blood sampling for DNA preparation in 170 elderly men. The DNA was bisulfite treated, and the methylation status of five CpG units in the AR promoter was analyzed using a high-throughput technique based on MALDI-TOF mass spectrometry. The degree of methylation of all the five investigated CpG units was strongly positively associated with the percent of lymphocytes in the PBL (r (s) = 0.17-0.49, P < 0.05). Furthermore, the PBL distribution-adjusted methylation status of a specific CpG unit in the AR promoter was significantly associated with body mass index (r (s) = 0.24) and other measures reflecting fat mass in elderly men. In conclusion, adjustment for PBL distribution needs to be done to be able to use DNA from whole blood for methylation analysis of the AR promoter and most likely also when investigating other promoters.
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- Hellman, Bo, et al.
(författare)
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Effects of external ATP on Ca(2+) signalling in endothelial cells isolated from mouse islets
- 2007
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 0969-711X .- 1559-0100. ; 32:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- External ATP is believed to initiate and propagate Ca2+ signals co-ordinating the insulin release pulses within and among the different islets in the pancreas. The possibility that islet endothelial cells participate in this process was evaluated by comparing the effects on [Ca2+]i of purinoceptor activation in these cells with those in β-cells. β-Cell-rich pancreatic islets were isolated from ob/ob mice and dispersed into single cells/aggregates. After culture with or without endothelial cell growth supplement (ECGS), the cytoplasmic Ca2+ concentration ([Ca2+]i) was measured with ratiometric fura-2 technique. Presence of ECGS or prolongation of culture (>5 days) resulted in proliferation of endothelial cells and altered their phenotype from rounded to elongated. Endothelial cells, preliminarily identified by attachment of Dynabeads coated with the Bandeiraea simplicifolia 1 lectin (BS-1), responded in a similar way as those stained with CD31 antibodies after measurements of [Ca2+]i. Spontaneous transients and oscillations of [Ca2+]i were seen in β-cells, but not in endothelial cells exposed to 20 mM glucose. Addition of ATP (10 μM) resulted in pronounced and more extended rise of [Ca2+]i in endothelial cells than in β-cells. The endothelial cells differed from the β-cells by also responding with a rise of [Ca2+]i to 10 μM UTP, but not to equimolar ADP and acetylcholine. The results support the idea of mutual interactions between islet endothelium and β-cells based on ATP-induced Ca2+ signals. It is suggested that the endothelial cells have a tonic inhibitory action on β-cell P2 purinoceptors resulting in impaired synchronization of the insulin release pulses.
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