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Table 1 Effect of AhR/CYP1A1 pathways on various species under diabetic conditions

From: Insight into the physiological and pathological roles of the aryl hydrocarbon receptor pathway in glucose homeostasis, insulin resistance, and diabetes development

DM

 

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

[58, 60]

  

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

[76, 80]

 

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

[113, 114, 152,], [172]

  

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]

[103, 105]

 

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

[108, 109]

 

Rats

Sprague–Dawley

Treatment with STZ

↑ DM associated with increased CYP1A1 activity levels

[173]