A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum
Abstract
:1. Introduction
2. Results
3. Discussion
4. Methods
4.1. Subjects
4.2. Study Design and Sample Collection
4.3. Determination of Intestinal CYP450 activities
4.4. Quantification of Intestinal CYP450 mRNAs and CYP450 Genotype Analysis
4.5. Determination of Proinflammatory Cytokine Levels
4.6. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameters | Non-T2D Patients | Patients with T2D |
---|---|---|
No. of subjects | 16 | 20 |
Sex: No. (%) M:F | 7:9 (44:56) | 8:12 (40:60) |
Age (years) | 57 ± 16 | 62 ± 11 |
BMI (kg m −2) | 25.8 ± 5.7 | 30.2 ± 6.6 * |
Insulin (pmol L−1) | 44.8 ± 26.2 | 188.2 ± 262.7 * |
Glycemia (mmol L−1) | 4.8 ± 0.5 | 7.1 ± 2.3 * |
HbA1C (%) | 5.4 ± 0.4 | 7.2 ± 1.0 * |
HOMA-IR | 1.4 ± 0.9 | 11.4 ± 25.8 * |
HOMA-β | 98 ± 50 | 151 ± 145 |
Time since diagnostic (years) | NA | 9.5 ± 5.8 |
Medication use, No. (%) of subjects | ||
Metformin | 0 | 13 (65) * |
Sulfonylurea | 0 | 7 (35) * |
DPP4-I | 0 | 3 (15) |
Insulin | 0 | 5 (25) |
Statins | 2 (13) | 9 (45) |
ACEI | 2 (13) | 4 (20) |
ARB | 2 (13) | 7 (35) |
CCB | 2 (13) | 4 (20) |
PPI | 10 (63) | 8 (40) |
β-Blockers | 2 (13) | 4 (20) |
Aspirin | 4 (26) | 8 (40) |
other NSAID | 3 (19) | 1 (5) |
Antidepressants | 1 (6) | 5 (25) |
Item | Non-T2D Patients (n = 15) | Patients with T2D (n = 20) | p-Value | Adjusted p-Value a |
---|---|---|---|---|
Drug Metabolizing Enzymes | ||||
CES-1 | 2.5 (1.3–3.7) | 2.8 (2.1–3.8) | 0.4 | 0.5 |
CES-2 | 2.1 (2.0–2.6) | 2.3 (2.1–2.6) | 0.8 | 0.9 |
CYP1A1 | 6.0 (1.5–15.2) | 6.2 (3.3–20.2) | 0.5 | 0.4 |
CYP2B6 | 4.1 (1.9–4.7) | 4.8 (3.4–8.9) | 0.3 | 0.2 |
CYP2C8 | 3.8 (1.8–6.2) | 2.7 (1.4–4.4) | 0.5 | 0.3 |
CYP2C9 | 9.0 (6.3–13.0) | 11.9 (8.9–14.7) | 0.051 | 0.09 |
CYP2C19 | 4.4 (3.3–5.2) | 4.3 (3.4–5.6) | 0.7 | 0.7 |
CYP2D6 | 2.4 (1.5–3.6) | 2.9 (1.6–5.3) | 0.1 | 0.1 |
CYP2E1 | 2.2 (0.9–6.8) | 1.6 (1.2–2.6) | 0.3 | 0.2 |
CYP2J2 | 1.8 (1.2–2.1) | 2.0 (1.5–2.5) | 0.3 | 0.3 |
CYP3A4 | 4.1 (2.9–5.9) | 4.6 (3.5–7.1) | 0.5 | 0.6 |
CYP3A5 | 3.9 (3.0–19.4) | 4.2 (3.5–8.1) | 0.3 | 0.3 |
Drug Transporters | ||||
ABCB1 | 1.5 (1.1–2.0) | 1.6 (1.2–1.9) | 0.7 | 0.5 |
ABCG2 | 2.7 (2.3–3.6) | 3.2 (2.8–4.1) | 0.2 | 0.2 |
OATP2B1 | 0.7 (0.6–0.9) | 0.9 (0.8–0.1) | 0.02* | 0.02 * |
Proinflammatory Cytokines | Non-T2D Patients (n = 16) | Patients with T2D (n = 20) | p-Value |
---|---|---|---|
IFN-γ | 3.80 ± 2.67 | 3.41 ± 2.15 | 0.98 |
IL-1β | 0.07 ± 0.07 | 0.09 ± 0.10 | 0.86 |
IL-6 | 0.99 ± 0.49 | 1.07 ± 0.94 | 0.35 |
TNF-α | 2.00 ± 0.36 | 2.71 ± 1.25 | 0.03 * |
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Gravel, S.; Panzini, B.; Belanger, F.; Turgeon, J.; Michaud, V. A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum. Int. J. Mol. Sci. 2019, 20, 3257. https://doi.org/10.3390/ijms20133257
Gravel S, Panzini B, Belanger F, Turgeon J, Michaud V. A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum. International Journal of Molecular Sciences. 2019; 20(13):3257. https://doi.org/10.3390/ijms20133257
Chicago/Turabian StyleGravel, Sophie, Benoit Panzini, Francois Belanger, Jacques Turgeon, and Veronique Michaud. 2019. "A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum" International Journal of Molecular Sciences 20, no. 13: 3257. https://doi.org/10.3390/ijms20133257