Pioglitazone Induced Gastric Acid Secretion

Rotte, Anand; Mack, Andreas F.; Bhandaru, Madhuri; Kempe, Daniela S.; Beier, Norbert; Scholz, Wolfgang; Dicks, Edith; Pötzsch, Sven; Kuhl, Dietmar; Läng, Florian

doi:10.1159/000233245

Cited by 13 publications

(7 citation statements)

References 40 publications

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“…The perfusion chamber was mounted on the stage of an inverted microscope (Zeiss Axiovert 135), which was used in the epifluorescence mode with a 409 oil immersion objective (Zeiss Neoplan, Germany). BCECF was successively excited at 490/10 and 440/10 nm, and the resultant fluorescent signal was monitored at 535/10 nm using an intensified charge-coupled device camera (Proxitronic, Germany) and specialized computer software (Metafluor, USA) [85]. Cells were outlined and monitored during the course of the measurements.…”

Section: Intracellular Phmentioning

confidence: 99%

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

et al. 2012

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Sustained increase of cardiac workload is known to trigger cardiac remodeling with eventual development of cardiac failure. Compelling evidence points to a critical role of enhanced cardiac Na(+)/H(+) exchanger (NHE1) activity in the underlying pathophysiology. The signaling triggering up-regulation of NHE1 remained, however, ill defined. The present study explored the involvement of the serum- and glucocorticoid-inducible kinase Sgk1 in cardiac remodeling due to transverse aortic constriction (TAC). To this end, experiments were performed in gene targeted mice lacking functional Sgk1 (sgk1 (-/-)) and their wild-type controls (sgk1 (+/+)). Transcript levels have been determined by RT-PCR, cytosolic pH (pH( i )) utilizing 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF) fluorescence, Na(+)/H(+) exchanger activity by the Na(+)-dependent realkalinization after an ammonium pulse, ejection fraction (%) utilizing cardiac cine magnetic resonance imaging and cardiac glucose uptake by PET imaging. As a result, TAC increased the mRNA expression of Sgk1 in sgk1 (+/+) mice, paralleled by an increase in Nhe1 transcript levels as well as Na(+)/H(+) exchanger activity, all effects virtually abrogated in sgk1 (-/-) mice. In sgk1 (+/+) mice, TAC induced a decrease in Pgc1a mRNA expression, while Spp1 mRNA expression was increased, both effects diminished in the sgk1 (-/-) mice. TAC was followed by a significant increase of heart and lung weight in sgk1 (+/+) mice, an effect significantly blunted in sgk1 (-/-) mice. TAC increased the transcript levels of Anp and Bnp, effects again significantly blunted in sgk1 (-/-) mice. TAC increased transcript levels of Collagen I and III as well as Ctgf mRNA and CTGF protein abundance, effects significantly blunted in sgk1 (-/-) mice. TAC further decreased the ejection fraction in sgk1 (+/+) mice, an effect again attenuated in sgk1 (-/-) mice. Also, cardiac FDG-glucose uptake was increased to a larger extent in sgk1 (+/+) mice than in sgk1 (-/-) mice after TAC. These observations point to an important role for SGK1 in cardiac remodeling and development of heart failure following an excessive work load.

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Section: Intracellular Phmentioning

confidence: 99%

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

et al. 2012

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“…After loading, the chamber was flushed for 5 min with Ringer's solution to remove any de-esterified dye. The perfusion chamber was mounted on the stage of an inverted microscope (Zeiss Axiovert 135), which was used in the epifluorescence mode with a ×40 oil immersion objective (Zeiss Neoplan, Germany) [27][28][29][30][31]. BCECF was successively excited at 490/10 and 440/10 nm, and the resultant fluorescent signal was monitored at 535/10 nm using an intensified chargecoupled device camera (Proxitronic, Germany) and specialized computer software (Metafluor, USA).…”

Section: Intracellular Phmentioning

confidence: 99%

“…The results from each cell were averaged and taken for final analysis. Intensity ratio (490/ 440) data were converted into pH i values using the high-K + /nigericin calibration technique [28]. To this end, the cells were perfused at the end of each experiment for 5 min with standard high-K + /nigericin (10 μg/ml) solution (pH 7.0).…”

Section: Intracellular Phmentioning

confidence: 99%

Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Bhandaru

Yang

Rotte

et al. 2011

Pflugers Arch - Eur J Physiol

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Dendritic cells (DCs) are antigen-presenting cells decisive in primary immune responses and establishment of immunological memory. They are activated by bacterial lipopolysaccharides (LPS), which lead to activation of Na(+)/H(+) exchanger activity, cell swelling, reactive oxygen species (ROS) formation, and migration. The effects require functional phosphoinositide 3 kinase and are paralleled by Akt phosphorylation. The present study explored the putative involvement of the Akt isoform Akt2. To this end, experiments were performed in DCs isolated from bone marrow of mice lacking functional Akt2/PKBß (akt2 (-/-)) and respective wild-type animals (akt2 (+/+)). Based on BCECF fluorescence, cytosolic pH (pH(i)) was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. Transient exposure to NH(4)Cl was followed by profound cytosolic acidification in both genotypes. Subsequent re-alkalinization was largely dependent on Na(+) thus reflecting Na(+)/H(+) exchanger activity and was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. According to forward scatter in FACS analysis, cell volume was significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. Exposure of DCs to LPS led within 4 h to significant increases of Na(+)/H(+) exchanger activity, cell volume, ROS production, and migration in akt2 (+/+) mice, and its effects were significantly blunted in akt2 (-/-) DCs. The present observations disclose a role of Akt2 in the regulation of pH(i), cell volume, ROS production, and migration in dendritic cells.

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“…SGK1 is not required for the maintenance of basal gastric acid secretion but substantially contributes to the stimulation of gastric acid secretion by glucocorticoids, PPARgamma agonists or adenomatous polyposis coli (APC) deficiency [74][75][76]. SGK1 is at least partially effective through upregulation of KCNQ1 channels, which fosters the recycling of K ?…”

Section: Introductionmentioning

confidence: 99%

Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport

Läng

Vallon

2011

Clin Exp Nephrol

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Serum- and glucocorticoid inducible-kinase 1 (SGK1) is an early gene transcriptionally upregulated by cell stress such as cell shrinkage and hypoxia and several hormones including gluco- and mineralocorticoids. It is activated by insulin and growth factors. SGK1 is a powerful regulator of a wide variety of channels and transporters. The present review describes the role of SGK1 in the regulation of potassium (K(+)) channels, K(+) transporters and K(+) homeostasis. SGK1-regulated K(+) channels include renal outer medullary K+ channel, Kv1.3, Kv1.5, KCNE1/KCNQ1, KCNQ4 and, via regulation of calcium (Ca(2+)) entry, Ca(2+)-sensitive K(+) channels. SGK1-sensitive transporters include sodium-potassium-chloride cotransporter 2 and sodium/potassium-adenosine triphosphatase. SGK1-dependent regulation of K(+) channels and K(+) transport contributes to the stimulation of renal K(+) excretion following high K(+) intake, to insulin-induced cellular K(+) uptake and hypokalemia, to inhibition of insulin release by glucocorticoids, to stimulation of mast cell degranulation and gastric acid secretion, and to cardiac repolarization. Thus, SGK1 has a profound effect on K(+) homeostasis and on a multitude of K(+)-sensitive cellular functions.

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Pioglitazone Induced Gastric Acid Secretion

Cited by 13 publications

References 40 publications

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

Sgk1 sensitivity of Na+/H+ exchanger activity and cardiac remodeling following pressure overload

Regulation of Na+/H+ exchanger in dendritic cells by Akt2

Serum- and glucocorticoid-inducible kinase 1 in the regulation of renal and extrarenal potassium transport

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