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Impact of type 2 di...
Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity
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- Kvitne, K. E. (författare)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway.
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- Åsberg, A. (författare)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, Oslo, Norway.
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- Johnson, L. K. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.
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- Wegler, Christine (författare)
- Uppsala universitet,Institutionen för farmaci,AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab CVRM, DMPK,Res & Early Dev, Gothenburg, Sweden
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- Hertel, J. K. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab
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- Karlsson, Cecilia (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine,AstraZeneca, BioPharmaceut R&D, Late Stage Dev Cardiovasc Renal & Metab CVRM, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
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- Andersson, S. (författare)
- AstraZeneca, R&D, Discovery Sci, Oligonucleotide Discovery, Gothenburg, Sweden.
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- Sandbu, R. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Vestfold Hosp Trust, Dept Surg, Tonsberg, Norway.
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- Skovlund, E. (författare)
- Norwegian Univ Sci & Technol, Dept Publ Hlth & Nursing, NTNU, Trondheim, Norway.
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- Christensen, H. (författare)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway.
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- Jansson-Löfmark, R. (författare)
- AstraZeneca, BioPharmaceut R&D, Cardiovasc Renal & Metab CVRM, DMPK,Res & Early Dev, Gothenburg, Sweden.
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- Hjelmesæth, J. (författare)
- Vestfold Hosp Trust, Morbid Obes Ctr, Tonsberg, Norway.;Univ Oslo, Inst Clin Med, Dept Endocrinol Morbid Obes & Prevent Med, Oslo, Norway.
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- Robertsen, I. (författare)
- Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway.
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Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway Univ Oslo, Dept Pharm, Sect Pharmacol & Pharmaceut Biosci, Oslo, Norway.;Oslo Univ Hosp, Dept Transplantat Med, Oslo, Norway. (creator_code:org_t)
- 2022-09-08
- 2022
- Engelska.
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Ingår i: Clinical and Translational Science. - : Wiley. - 1752-8054 .- 1752-8062. ; 15:11, s. 2685-2696
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Previous studies have not accounted for the close link between type 2 diabetes mellitus (T2DM) and obesity when investigating the impact of T2DM on cytochrome P450 (CYP) activities. The aim was to investigate the effect of T2DM on in vivo activities and protein expressions of CYP2C19, CYP3A, CYP1A2, and CYP2C9 in patients with obesity. A total of 99 patients from the COCKTAIL study (NCT02386917) were included in this cross-sectional analysis; 29 with T2DM and obesity (T2DM-obesity), 53 with obesity without T2DM (obesity), and 17 controls without T2DM and obesity (controls). CYP activities were assessed after the administration of a cocktail of probe drugs including omeprazole (CYP2C19), midazolam (CYP3A), caffeine (CYP1A2), and losartan (CYP2C9). Jejunal and liver biopsies were also obtained to determine protein concentrations of the respective CYPs. CYP2C19 activity and jejunal CYP2C19 concentration were 63% (−0.39 [95% CI: −0.82, −0.09]) and 40% (−0.09 fmol/μg protein [95% CI: −0.18, −0.003]) lower in T2DM-obesity compared with the obesity group, respectively. By contrast, there were no differences in the in vivo activities and protein concentrations of CYP3A, CYP1A2, and CYP2C9. Multivariable regression analyses also indicated that T2DM was associated with interindividual variability in CYP2C19 activity, but not CYP3A, CYP1A2, and CYP2C9 activities. The findings indicate that T2DM has a significant downregulating impact on CYP2C19 activity, but not on CYP3A, CYP1A2, and CYP2C9 activities and protein concentrations in patients with obesity. Hence, the effect of T2DM seems to be isoform-specific. © 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
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Kvitne, K. E.
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Åsberg, A.
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Johnson, L. K.
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Wegler, Christin ...
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Hertel, J. K.
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Artursson, Per
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Karlsson, Cecili ...
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Andersson, S.
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Sandbu, R.
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Skovlund, E.
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Christensen, H.
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Jansson-Löfmark, ...
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Hjelmesæth, J.
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Robertsen, I.
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