Serum arylhydrocarbon receptor transactivating activity is elevated in type 2 diabetic patients with diabetic nephropathy

Abstract

Aims/Introduction: Evidence is emerging that exposure to persistent organic pollutants (POPs) is a risk factor for obesity-related diseases and for diabetes mellitus (DM). We found that POPs could be measured by a cell-based arylhydrocarbon receptor (AhR)-dependent reporter assay. We tested if serum AhR transactivating (AHRT) activities are a risk factor for diabetic nephropathy in people with type 2 diabetes. Materials and Methods: We enrolled diabetic patients with normoalbuminuria (n = 36), microalbuminuria (n = 29), macroalbuminuria (n = 8) and end-stage renal disease (n = 31). Sera were tested for their AHRT activities, which were standardized by an AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and expressed as TCDD equivalents (TCDDeq pmol/L). Results: Mean serum AHRT activities were higher in patients with microalbuminuria (40.1 -7.1 pmol/L), macroalbuminuria (37.4 -5.5 pmol/L) and end-stage renal disease (59.1 -20.0 pmol/L) than in subjects with normoalbuminuria (12.7 -5.4 pmol/L; P < 0.05 for all comparisons). Serum AhR ligands showed a correlation with estimated glomerular filtration rate (eGFR; r = -0.663, P < 0.001), serum creatinine level (r = 0.635, P < 0.001), systolic blood pressure (r = 0.223, P = 0.026), glycated hemoglobim (r = 0.339, P < 0.001) and diabetic duration (r = 0.394, P < 0.001). In a multiple regression analysis, diabetic nephropathy was found to be an independent risk factor for higher AHRT activity after controlling for the confounding factors. Conclusions: The present findings suggest serum AHRT activity, thus serum AhR ligands, is a risk factor for diabetic nephropathy. Further studies are required to clarify if an accumulation of POPs in the body is causally related to diabetic nephropathy. (J Diabetes Invest,

Cyp3a11‐mediated testosterone‐6β‐hydroxylation decreased, while UGT1a9‐mediated propofol O‐glucuronidation increased, in mice with diabetes mellitus

“…The liver UGT activity can be regulated by nuclear receptors. It has been reported that Ugt1a9 mRNA expression in the liver was markedly induced by activators of the aryl hydrocarbon receptor (AhR) , and the serum AhR ligand activities are higher in T2DM . Therefore, the significant increase in UGT1A9 activity observed in this study may be related to the activation of AhR in the diabetes mice model.…”

Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease

“…Higher levels of serum AHR agonists have previously been reported in smokers, 32 as well as in patients with diabetes, 33 especially with severe diabetic nephropathy. 34 The authors suggested increased level of serum AHR agonists as a risk factor for the progression of kidney disease. Indeed, the activation of AHR could lead to the impairment of renal function by podocyte aggression.…”

Metabolic syndrome and the environmental pollutants from mitochondrial perspectives

“…Those findings suggest they could be employed as a diagnostic marker of metabolic syndrome and T2DM. In fact, patients with complications from DM had higher serum AhR ligands levels, suggesting they might contribute to the development of diabetic complications as well [75].…”