ArticleDrug metabolism and disposition: the biological fate of chemicals2011
Diabetes mellitus reduces activity of human UDP-glucuronosyltransferase 2B7 in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 40 citations in OpenAlex.
- The Triangular Interaction Between Dietary Polyphenols, Gut Microbiota and Type 2 Diabetes.International journal of molecular sciences · 2026Review
- Metabolomic Profiling of Tongue Coating Reveals Potential Molecular Features Linked to Type 2 Diabetes Progression.International journal of molecular sciences · 2026Article
- Morusin as a drug candidate: opportunities, limitations, and the path toward clinical translation.Frontiers in pharmacology · 2025Review
- Integrative RNA-seq and CLIP-seq analysis revealsFrontiers in physiology · 2025Article
- Metabolic Profiling and Investigation of the Modulatory Effect ofAntioxidants (Basel, Switzerland) · 2023Article
- Analysis of in vitro and in vivo metabolism of zidovudine and gemfibrozil in trans-chromosomic mouse line expressing human UGT2 enzymes.Pharmacology research & perspectives · 2022Article
- Review
- The Functionality of UDP-Glucuronosyltransferase Genetic Variants and their Association with Drug Responses and Human Diseases.Journal of personalized medicine · 2021Review
- Mycophenolic Acid and Its Metabolites in Kidney Transplant Recipients: A Semimechanistic Enterohepatic Circulation Model to Improve Estimating Exposure.Journal of clinical pharmacology · 2018Article
- Evidence of glucuronidation of the glycation product LW-1: tentative structure and implications for the long-term complications of diabetes.Glycoconjugate journal · 2018Article
- Alterations in the gene expression of drug and arachidonic acid-metabolizing Cyp450 in the livers of controlled and uncontrolled insulin-dependent diabetic mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2018Article
- Identification and validation of the microRNA response elements in the 3'-untranslated region of the UDP glucuronosyltransferase (UGT) 2B7 and 2B15 genes by a functional genomics approach.Biochemical pharmacology · 2017Article
- Clinical Pharmacokinetics and Pharmacodynamics of Antihyperglycemic Medications in Children and Adolescents with Type 2 Diabetes Mellitus.Clinical pharmacokinetics · 2017Review
- Non-alcoholic fatty liver disease (NAFLD) - pathogenesis, classification, and effect on drug metabolizing enzymes and transporters.Drug metabolism reviews · 2017Review
- Altered Transport and Metabolism of Phenolic Compounds in Obesity and Diabetes: Implications for Functional Food Development and Assessment.Advances in nutrition (Bethesda, Md.) · 2016Review
- Clinical pharmacokinetics and pharmacodynamics of dapagliflozin, a selective inhibitor of sodium-glucose co-transporter type 2.Clinical pharmacokinetics · 2014 · on this mapReview
- Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism.Xenobiotica; the fate of foreign compounds in biological systems · 2013Article
- The effect of moderate hepatic impairment on the pharmacokinetics of ipragliflozin, a novel sodium glucose co-transporter 2 (SGLT2) inhibitor.Clinical drug investigation · 2013Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mycophenolic acid (MPA) is an immunosuppressive agent commonly used after organ transplantation. Altered concentrations of MPA metabolites have been reported in diabetic kidney transplant recipients, although the reason for this difference is unknown. We aimed to compare MPA biotransformation and UDP-glucuronosyltransferase (UGT) expression and activity between liver (n = 16) and kidney (n = 8) from diabetic and nondiabetic donors. Glucuronidation of MPA, as well as the expression and probe substrate activity of UGTs primarily responsible for MPA phenol glucuronide (MPAG) formation (UGT1A1 and UGT1A9), and MPA acyl glucuronide (AcMPAG) formation (UGT2B7), was characterized. We have found that both diabetic and nondiabetic human liver microsomes and kidney microsomes formed MPAG with similar efficiency; however, AcMPAG formation was significantly lower in diabetic samples. This finding is supported by markedly lower glucuronidation of the UGT2B7 probe zidovudine, UGT2B7 protein, and UGT2B7 mRNA in diabetic tissues. UGT genetic polymorphism did not explain this difference because UGT2B7*2 or *1c genotype were not associated with altered microsomal UGT2B7 protein levels or AcMPAG formation. Furthermore, mRNA expression and probe activities for UGT1A1 or UGT1A9, both forming MPAG but not AcMPAG, were comparable between diabetic and nondiabetic tissues, suggesting the effect may be specific to UGT2B7-mediated AcMPAG formation. These findings suggest that diabetes mellitus is associated with significantly reduced UGT2B7 mRNA expression, protein level, and enzymatic activity of human liver and kidney, explaining in part the relatively low circulating concentrations of AcMPAG in diabetic patients.
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