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18 results on '"Rinne, Valtteri"'

9. Physiologically Based Pharmacokinetic/Pharmacodynamic Model for the Treatment of Dengue Infections Applied to the Broad Spectrum Antiviral Soraphen A

Author

Rox, Katharina, primary, Heyner, Maxi, additional, Krull, Jana, additional, Harmrolfs, Kirsten, additional, Rinne, Valtteri, additional, Hokkanen, Juho, additional, Perez Vilaro, Gemma, additional, Díez, Juana, additional, Müller, Rolf, additional, Kröger, Andrea, additional, Sugiyama, Yuichi, additional, and Brönstrup, Mark, additional

Published
2021
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12. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes

Author

Aatsinki, Sanna-Mari, Elkhwanky, Mahmoud-Sobhy, Kummu, Outi, Karpale, Mikko, Buler, Marcin, Viitala, Pirkko, Rinne, Valtteri, Mutikainen, Maija, Tavi, Pasi, Franko, Andras, Wiesner, Rudolf J., Chambers, Kari T., Finck, Brian N., Hakkola, Jukka, Aatsinki, Sanna-Mari, Elkhwanky, Mahmoud-Sobhy, Kummu, Outi, Karpale, Mikko, Buler, Marcin, Viitala, Pirkko, Rinne, Valtteri, Mutikainen, Maija, Tavi, Pasi, Franko, Andras, Wiesner, Rudolf J., Chambers, Kari T., Finck, Brian N., and Hakkola, Jukka

Abstract

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation-responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor alpha (ERR alpha)-dependent manner. However, PGC-1 alpha knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1 alpha-ERR alpha pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway.

Published
2019

13. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes

Author

Aatsinki, Sanna-Mari, primary, Elkhwanky, Mahmoud-Sobhy, additional, Kummu, Outi, additional, Karpale, Mikko, additional, Buler, Marcin, additional, Viitala, Pirkko, additional, Rinne, Valtteri, additional, Mutikainen, Maija, additional, Tavi, Pasi, additional, Franko, Andras, additional, Wiesner, Rudolf J., additional, Chambers, Kari T., additional, Finck, Brian N., additional, and Hakkola, Jukka, additional

Published
2019
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14. Fasting-Induced Transcription Factors Repress Vitamin D Bioactivation, a Mechanism for Vitamin D Deficiency in Diabetes.

Author

Viitala, Pirkko, Elkhwanky, Mahmoud-Sobhy, Kummu, Outi, Karpale, Mikko, Buler, Marcin, Hakkola, Jukka, Aatsinki, Sanna-Mari, Rinne, Valtteri, Mutikainen, Maija, Tavi, Pasi, Wiesner, Rudolf J., Franko, Andras, Chambers, Kari T., and Finck, Brian N.

Subjects
VITAMIN D deficiency, VITAMIN D, TRANSCRIPTION factors, VITAMIN D metabolism, PEROXISOME proliferator-activated receptors
Abstract

Low 25-hydroxyvitamin D levels correlate with the prevalence of diabetes; however, the mechanisms remain uncertain. Here, we show that nutritional deprivation-responsive mechanisms regulate vitamin D metabolism. Both fasting and diabetes suppressed hepatic cytochrome P450 (CYP) 2R1, the main vitamin D 25-hydroxylase responsible for the first bioactivation step. Overexpression of coactivator peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), induced physiologically by fasting and pathologically in diabetes, resulted in dramatic downregulation of CYP2R1 in mouse hepatocytes in an estrogen-related receptor α (ERRα)-dependent manner. However, PGC-1α knockout did not prevent fasting-induced suppression of CYP2R1 in the liver, indicating that additional factors contribute to the CYP2R1 repression. Furthermore, glucocorticoid receptor (GR) activation repressed the liver CYP2R1, suggesting GR involvement in the regulation of CYP2R1. GR antagonist mifepristone partially prevented CYP2R1 repression during fasting, suggesting that glucocorticoids and GR contribute to the CYP2R1 repression during fasting. Moreover, fasting upregulated the vitamin D catabolizing CYP24A1 in the kidney through the PGC-1α-ERRα pathway. Our study uncovers a molecular mechanism for vitamin D deficiency in diabetes and reveals a novel negative feedback mechanism that controls crosstalk between energy homeostasis and the vitamin D pathway. [ABSTRACT FROM AUTHOR]

Published
2019
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17. Oxadiazole-carbonylaminothioureas as SIRT1 and SIRT2 Inhibitors

Author

Huhtiniemi, Tero, primary, Suuronen, Tiina, additional, Rinne, Valtteri M., additional, Wittekindt, Carsten, additional, Lahtela-Kakkonen, Maija, additional, Jarho, Elina, additional, Wallén, Erik A. A., additional, Salminen, Antero, additional, Poso, Antti, additional, and Leppänen, Jukka, additional

Published
2008
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18. Influence of MK-467, a Peripherally Acting α2-Adrenoceptor Antagonist on the Disposition of Intravenous Dexmedetomidine in Dogs

Author

Honkavaara, Juhana, Restitutti, Flavia, Raekallio, Marja, Salla, Kati, Kuusela, Erja, Ranta-Panula, Ville, Rinne, Valtteri, Vainio, Outi, and Scheinin, Mika

Abstract

Growing evidence supports the use of (2R-trans)-N-(2-(1,3,4,7,12b-hexahydro-2'-oxo-spiro(2H-benzofuro(2,3-a)quinolizine-2,4'-imidazolidin)-3'-yl)ethyl) methanesulfonamide (MK-467), a peripherally acting α2-adrenoceptor antagonist, in conjunction with the sedative-anesthetic agent dexmedetomidine in animals to avoid hemodynamic compromise. We evaluated the possible effects of different doses of MK-467 on the plasma concentrations of dexmedetomidine in eight beagle dogs. Both drugs were administered intravenously. Each dog received five treatments: dexmedetomidine alone (10 μg/kg), MK-467 alone (250 μg/kg), and dexmedetomidine (10 μg/kg) combined with different doses of MK-467 (250, 500, and 750 μg/kg) in a randomized, crossover fashion. Selected pharmacokinetic parameters were calculated. The area under the time-concentration curve of dexmedetomidine was significantly greater after dexmedetomidine alone (by 101 ± 20%, mean ± 95% confidence interval) compared with that after dexmedetomidine and 250 μg/kg MK-467. Increasing the dose of the antagonist had no further effect on the exposure to dexmedetomidine. The apparent volume of distribution of dexmedetomidine was significantly smaller after dexmedetomidine alone compared with that after all treatments that included MK-467. Dexmedetomidine (10 μg/kg) did not significantly influence the plasma concentrations of MK-467 (250 μg/kg). The results suggest that the peripherally acting α2-adrenoceptor antagonist MK-467 markedly influenced the early disposition of dexmedetomidine without obvious effects on the later plasma concentrations of the drug.

Published
2012

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