Table 1.
Physiological role of TXNIP in normal, obese, STZ, endotoxin, ischemia, and diabetic conditions. The key physiological findings based on genetic knockout (KO) or mutated mice are summarized. ↑ Up-regulation/Enhanced function, ↓ Down-regulation/Reduced function.
| Tissue/Cell Type | TXNIP Function | Key Signal | TXNIP Whole Body KO/Mutant | TXNIP Tissue Specific KO/Mutant | Reference |
|---|---|---|---|---|---|
| β cells (Normal) |
Apoptosis↑ Glucose-stimulated insulin secretion (GSIS)↓ |
Mitochondria metabolism TRX/TRX2/ROS MAFA/miR-204 IAPP/miR-24a Zeb1/miR-200 |
GSIS↑ Hyperinsulinemia↑ |
β cell mass↑ Apoptosis↓ |
[11,12,41,86,87,88] |
| β cells (STZ/Obese/Diabetic) |
Apoptosis↑ Glucose-stimulated insulin secretion (GSIS)↓ β cells hypertrophy↓ |
Mitochondria metabolism/uncoupling AKT/Bcl-2 UPR/ER stress |
GSIS↑ Hyperinsulinemia↑ Apoptosis↓ |
Hyperinsulinemia↑ β cell mass↑ Apoptosis↓ |
[12,13,14,78,79] |
| Skeletal muscle (Normal) |
Insulin sensitivity/Glucose uptake↓ | AKT/GLUT4 PTEN AMPK |
Insulin Sensitivity↑ | Insulin Sensitivity↑ | [12,16,32,91,130] |
| Skeletal muscle (Obese/Diabetic) |
Insulin sensitivity/Glucose uptake↓ (Insulin Resistance↑) | AKT/GLUT4 PTEN |
Insulin Sensitivity↑ | [12,16] | |
| Adipose (Normal) |
Insulin sensitivity/Glucose uptake, Adipogenesis↓ | AKT/GLUT4 | Insulin Sensitivity↑ | [11,12,16,32] | |
| Adipose (Obese/Diabetic) |
Insulin sensitivity/Glucose uptake↓ (Insulin Resistance↑) | AKT/GLUT4 | Insulin Sensitivity↑ | Insulin Sensitivity↑ | [12,15] |
| Liver (Normal) |
Gluconeogenesis↑ Lipogenesis↓ |
FOXO1 SREBP PPARα AKT |
Abnormal steatosis in fasting | Normal glycemica, Hypoglycemia in fasting | [7,8,9,10,11,16,43,98,99] |
| Liver (Obese/Diabetic) |
Gluconeogenesis↑ Lipogenesis↓ |
PRMT1/PGC1a | Lipogenesis↓ | [12] | |
| Immune cells (Normal) |
Inflammation↓ Tumor rejection↑ Hematopoetic Stem Cells↓ |
NLRP3 inflammasome TRX/ROS P38 |
NK cells↓ T-cell response↓ |
[44,45,46,47,48] | |
| Immune cells (Obese/Diabetic/Endotoxin) |
Inflammation↓ | PI3K/ROS NO |
Resistant to P. aeruginosa-induced bacteremic shock Metabolic disordering by LPS |
[46,47] | |
| Brain (Normal) |
Glucose uptake↓ | TRX/ROS AKT/GLUT4 |
Glucose uptake↑ | [32] | |
| Brain (Obese/Diabetic) |
Energy expenditure↑ Adipogenesis↓ Body Weight↑ Insulin resistance↑ |
TRX/ROS | Hypothalamus:Body Weight↓ Insulin resistance↓ AgRP Neuron: Energy expenditure↓ Adipogenesis↓ |
[103,104,105] | |
| Heart (Normal) |
Fatty Acid oxidation↓ Glucose Oxidatation↑ |
miR33/AMPKα | Fatty Acid oxidation↑ Glucose Oxidatation↓ |
[131] | |
| Heart (Obese/Diabetic/Ischemia) |
Mitochondria↑ | Resistant for ischemia-reperfusion injury | [128,129,130] |