Recently, there have been efforts to use ultraviolet-B radiation (UV-B) as a biotechnological tool in greenhouses. Leafy species are mainly considered for their ability to synthesize glucosinolates and are valued as baby salads. They also have a remarkable concentration of chemically diverse flavonoid glycosides.
View Article and Find Full Text PDFContext: Depending on its lipolytic activity, glucagon plays a promising role in obesity treatment. Glucagon-induced growth hormone (GH) release can promote its effect on lipid metabolism, although the underlying mechanisms have not been well-defined.
Objective: The present study highlights the glucagon effect on the GH/insulinlike growth factor 1 (IGF-1)/IGF-binding protein (IGFBP) axis in vivo and in vitro, taking into consideration insulin as a confounding factor.
Scope: Nasturtium plants contain the glucosinolate glucotropaeolin and its corresponding breakdown product benzyl isothiocyanate (BITC), the latter being intensively studied with regard to cancer chemoprevention and anti-inflammatory properties. In addition, recent research has shown that isothiocyanates are able to activate the release of several gut hormones in vitro and in rodent studies. Here, we tested the effects of a dietary nasturtium administration on circulating levels of gut hormones in humans.
View Article and Find Full Text PDFNasturtium (Tropaeolum majus L.) contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC)-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1).
View Article and Find Full Text PDFThe flavones apigenin (4',5,7,-trihydroxyflavone) and luteolin (3',4',5,7,-tetrahydroxyflavone) are plant secondary metabolites with antioxidant, antiinflammatory, and anticancer activities. We evaluated their impact on cell signaling pathways related to insulin-resistance and type 2 diabetes. Apigenin and luteolin were identified in our U-2 OS (human osteosarcoma) cell screening assay for micronutrients triggering rapid intracellular translocation of the forkhead box transcription factor O1 (FOXO1), an important mediator of insulin signal transduction.
View Article and Find Full Text PDFSignaling through the mammalian target of rapamycin complex 1 (mTORC1) and its effectors the S6-kinases (S6K) in the hypothalamus is thought to be involved in nutrient sensing and control of food intake. Given the anatomical proximity of this pathway to circuits for the hormone ghrelin, we investigated the potential role of the mTORC1/S6K pathway in mediating the metabolic effects of ghrelin. We found that ghrelin promoted phosphorylation of S6K1 in the mouse hypothalamic cell line N-41 and in the rat hypothalamus after intracerebroventricular administration.
View Article and Find Full Text PDFBackground: Despite their beneficial effects on weight loss and blood lipids, high-protein (HP) diets have been shown to increase insulin resistance and diabetes risk, whereas high-cereal-fiber (HCF) diets have shown the opposite effects on these outcomes.
Objective: We compared the effects of isoenergetic HP and HCF diets and a diet with moderate increases in both cereal fibers and dietary protein (Mix diet) on insulin sensitivity, as measured by using euglycemic-hyperinsulinemic clamps with infusion of [6,6-(2)H(2)]glucose.
Design: We randomly assigned 111 overweight adults with features of the metabolic syndrome to 1 of 4 two-phased, 18-wk isoenergetic diets by group-matching.
Context And Objective: Inactivating mutations in the calcium-sensing receptor (CaSR) gene cause neonatal severe hyperparathyroidism and familial hypocalciuric hypercalcemia (FHH). The aims of the present study were the functional characterization of novel mutations of the CaSR found in FHH patients, the comparison of in vitro receptor function with clinical parameters, and the effect of the allosteric calcimimetic NPS R-568 on the signaling of mutant receptors.
Methods: Wild-type and mutant CaSRs (W530G, C568Y, W718X, M734R, L849P, Q926R, and D1005N) were expressed in human embryonic kidney 293 cells.
The intracellular enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts cortisone into the more active metabolite cortisol. Overexpression of 11beta-HSD1 was associated with features of the metabolic syndrome such as obesity or impaired glucose tolerance. Despite this considerable impact of 11beta-HSD1, the human 11beta-HSD1 promoter has not been described in detail yet.
View Article and Find Full Text PDFGlobal gene expression profiles of livers from mice, fed diets differing in alpha-tocopherol content, were compared using DNA microarray technology. Three hundred and eighty nine genes were found to significantly differ in their expression level by a factor of 2 or higher between the high and the low alpha-tocopherol group. Functional clustering using the EASE software identified 121 genes involved in transport processes.
View Article and Find Full Text PDFMetabolism of vitamin E is initiated by cytochrome P450 (CYP) enzymes usually involved in the metabolism of xenobiotics. Like other CYP substrates, vitamin E induced a reporter gene under the control of the pregnane X receptor (PXR) which regulates the expression of CYPs including CYP3A4. gamma-Tocotrienol, the most effective PXR activator, also induced endogenous CYP3A4 mRNA in HepG2 cells.
View Article and Find Full Text PDFSome 80 years after its discovery, vitamin E has experienced a renaissance which is as surprising as it is trivial. Although vitamin E is essential for reproduction, in rats at least, and deficiency causes neurological disorders in humans, the main interest in the last decades has concentrated on its antioxidant functions. This focus has highly underestimated the biological importance of vitamin E, which by far exceeds the need for acting as a radical scavenger.
View Article and Find Full Text PDFBackground: Glucocorticoids (GCs) are commonly used for long-term medication in immunosuppressive and anti-inflammatory therapy. However, the data describing gluco- and mineralo-corticoid (MC) properties of widely applied synthetic GCs are often based on diverse clinical observations and on a variety of in vitro tests under various conditions, which makes a quantitative comparison questionable.
Method: We compared MC and GC properties of different steroids, often used in clinical practice, in the same in vitro test system (luciferase transactivation assay in CV-1 cells transfected with either hMR or hGRalpha expression vectors) complemented by a system to test the steroid binding affinities at the hMR (protein expression in T7-coupled rabbit reticulocyte lysate).
Glucocorticoid (GC) and mineralocorticoid (MC) action in target tissues is determined by prereceptor metabolism by 11beta-hydroxysteroid-dehydrogenases (HSDs) and receptor transactivation. We characterized these parameters for steroids often used in clinical practice. HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes.
View Article and Find Full Text PDFJ Clin Endocrinol Metab
June 2003
Progesterone (P) is a potent antagonist of the human mineralocorticoid receptor (MR) in vitro. We have previously demonstrated effective downstream metabolism of P in the kidney. This mechanism potentially protects the MR from P action.
View Article and Find Full Text PDFThe 11beta-hydroxysteroid dehydrogenase (11beta-HSD) system plays a pivotal role in glucocorticoid (GC) and mineralocorticoid (MC) action. Although 11beta-HSD activities are important determinants for the efficacy of synthetic MCs and GCs, corresponding pharmacokinetic data are scanty. Therefore, we characterized 11beta-HSD profiles for a wide range of steroids often used in clinical practice.
View Article and Find Full Text PDFDue to high binding affinity of progesterone to the human mineralocorticoid receptor (hMR), progesterone competes with the natural ligand aldosterone. In order to analyse how homeostasis can be maintained by mineralocorticoid function of aldosterone at the MR, especially in the presence of elevated progesterone concentrations during the luteal phase and pregnancy, we investigated protective mechanisms such as the decrease of free progesterone by additional binding sites and progesterone metabolism in renal cells. As a prerequisite for sequestration of progesterone by binding to the human progesterone receptor (hPR) we demonstrated the existence of hPR expression in female and male kidney cortex and medulla at the level of transcription and translation.
View Article and Find Full Text PDFObjective: Progesterone binds to the human mineralocorticoid receptor (hMR) with nearly the same affinity as do aldosterone and cortisol, but confers only low agonistic activity. It is still unclear how aldosterone can act as a mineralocorticoid in situations with high progesterone concentrations, e.g.
View Article and Find Full Text PDFIt has been established that mucin-producing variants of different subtypes of pancreatic carcinomas, including the intraductal papillary and ductal mucinous tumors, have usually a more favorable prognosis. Intraductal papillary and ductal mucinous tumors have also been shown to ectopically express the intestinal mucin gene MUC2. The mechanism of the de novo expression of this gene in tumors may have potential implications for the modulation of its behavior.
View Article and Find Full Text PDFIn the present work we investigated the in vivo regulation of the mucin gene MUC2, which is overexpressed in all mucinous colorectal carcinomas. The inhibition of methylation by 5-azadeoxycytidine induces de novo expression of MUC2 in the colon carcinoma cell line COLO 205. The expression is retained in xenograft tissue and the cells give rise to MUC2-expressing tumours in nude mice.
View Article and Find Full Text PDFProgesterone (P) is a mineralocorticoid (MC)-antagonist in vitro. During pregnancy, plasma P concentrations exceed aldosterone concentrations at least 50-fold, but plasma aldosterone increases only 4-8-fold in a compensatory manner. Since the in vivo anti-MC activity of P seems to be only moderate, we hypothesized that P is metabolized by enzymes of MC target tissue similar to the way cortisol is metabolized by 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2 in order to protect the MC receptor.
View Article and Find Full Text PDFTo evaluate the hypothalamus as a possible site of metabolic modulation of GH secretion, we studied the GH response to insulin hypoglycemia (IHG) and nicotinic acid (NA)-induced FFA depression in the absence and presence of third ventricular (ivt) infusions of glucose, oleic acid (Ol-Ac), or beta-hydroxybutyrate (beta OHB). Four rhesus monkeys had been prepared for chronic remote iv and ivt infusions as well as blood sampling from the adjacent room. Statistical evaluation used a two-way analysis of variance and individual comparisons with Tukey's Studentized range test.
View Article and Find Full Text PDFThe biological activity and the fate of SV40 DNA (minichromosomes, DNA I, DNA II, DNA III) were tested in culture cells by immunofluorescence staining and blot analysis. Following microinjection of 2-4 circular SV40 molecules (minichromosomes, DNA I, DNA II) into the cytoplasm or the nuclei of monkey and rat cells, T- and V-antigen synthesis was demonstrable in nearly every recipient cell. Only linear DNA induced T-antigen synthesis with a very low efficiency after cytoplasmic injection.
View Article and Find Full Text PDFMicroinjection of early simian virus 40 (SV40) DNA fragments has shown that maximal transformation of rat cells (Ref 52) is a property of the second SV40 T-antigen exon. Expression of this particular T-antigen region was obtained by coinjection of the Taq/Bam DNA fragment with the early promoter/enhancer HpaII/BglI fragment. Microinjection of the DNA fragment mixture induced two categories of transformants; namely, maximally and minimally transformed cells.
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