DM | Â | Species | Treatment | Effect of AhR/CYP1A1 pathway in glucose hemostasis, insulin secretion, and DM | References |
---|---|---|---|---|---|
T1DM | Mice | Mice | NOD-mice | Pancreatic endocrine cells appear in crosstalk with gut microbiota via AMPs AMPs halt pancreatic inflammation AhR was expressed in intestinal ILCs, establishing that AhR–ILC axis exists to maintain gut integrity, which impacts T1DM progression | |
 |  | C57BL/6 mice | TCDD | AhR activation promoted Treg induction and development by binding to the Foxp3 + promoter | [53] |
T2DM | Human | Pancreatic endocrine cell line | TCDD | ↓ insulin secretion ↓ plasma insulin level ↑ β-cells death | [46] |
 |  | hESC cells | Low dose TCDD | Impaired pancreatic lineage differentiation and AMPK pathway leading to impaired pancreatic development and function | [70] |
 |  | Aortic endothelial cells (ECs) | High glucose levels | ↑ AhR activity leads to increased TSP-1, which is involved in the development of diabetic vascular complications AhR interacts with Egr-1 and AP-2 → endothelial dysfunction and microvascular complications | [72] |
 |  | Human Sera | Serum TCDD levels | Korean diabetic patients have higher serum AhR ligand TCDD levels > non-diabetics mitochondrial dysfunction leads to the pathogenesis of insulin resistance | |
 | Mice | Hepa-1c1c7 (cell line) | β-NF, TCDD, | ↑ insulin sensitivity, ↓ PPAR-α expression and altered G6Pase and PEPCK in AhR KO mice ↑ Cyp1a1 and PPAR-α expression | [102] |
 |  | Mice | TCDD | ↓ G6Pase & PEPCK enzymes ↓ adipogenesis ↑ ROS levels in the liver mitochondria leading to hepatic insulin resistance | |
 |  | Obese mice | α-NF | ↓ PPAR-α activity expression of obesity markers, stearoyl-CoA desaturase one and phosphoprotein 1 | [117] |
 |  | Mice | AhR KO | ↓ glucose levels in plasma and liver ↓ alanine levels (substrate in the gluconeogenesis during fasting), muscle and liver disrupted glucose and fatty acid metabolisms | [124] |
 |  | Mice | STZ | ↓ expression of COX-2 in the kidneys under diabetic conditions, thus highlighting a link between AhR and diabetic nephropathy | [149] |
 |  | Kunming diabetic mice | Alizarin | ↓ glucose levels, lipid profile, and oxidative stress | [150] |
 |  | C57BL/6 | PCBs α-NF, resveratrol | ↑ impairment of glucose and insulin ↑ inflammatory mediators, TNF-α in adipose tissue ↓ glucose intolerance and insulin secretion | [103] |
 | Guinea pigs | Guinea pigs | Transient TCDD exposure | ↓ glucose uptake in the pancreas and adipose tissue, owing to the reduced number of glucose transporting proteins on the plasma membrane of these organs ↓ GLUT genes via AhR-dependent mechanism ↓ lipogenesis & gluconeogenesis, dysregulated lipoprotein lipase activity, disrupted insulin production and fatty acid synthesis | |
 | Rats | Sprague–Dawley | Treatment with STZ | ↑ DM associated with increased CYP1A1 activity levels | [173] |