Table 4.
List of novel targets with emerging implications related to insulin receptor signaling
| Insulin receptor signaling | Target tissue | Effect/ potential role | Reference |
|---|---|---|---|
| HCF-1 | Hepatocyte (human, mice) | HCF-1-dependent pathway regulating Glucose and lipid metabolism | 516 |
| IRS/PTP1B | Cerebral microvascular endothelial cells (mice) | Hyperinsulinemia affects insulin receptor signaling and internalization of endothelial cells | 517 |
| SMPDL3b/C1P/Cav-1 | kidney cortexes (rats), podocytes (human) | Inducing glucose and lipid metabolism, protein synthesis | 518 |
| IRS/IGF1/SRF | Myocardium (mice) | Affecting autophagy and apoptosis of cardiomyocytes | 519 |
| SDF-1/CXCR4 | Primary endothelial cells (human), CD31 + cells (mice) | Affecting immune cell recruitment to the vascular wall or tissue parenchyma | 520 |
| miR-15b, miR-16, miR-30b/IRS2 | Endothelial cells (human) | IRS2 and eNOS in ECs are ceRNAs and related to the Akt signal pathway | 521 |
| IRS | Renal hemodynamics (mice) | stimulation of renal functions and renal hemodynamics | 522 |
| IRS/p53/KLF4 | Vascular smooth muscle cells (mice) | IRS-1/p53 affects the progression of atherosclerotic lesions in hyperglycemia | 523 |
| QKI-7 | Endothelial cells (human) | Promotes mRNA degradation of essential genes for EC function | 524 |
| EPDR1 | Endothelial cells (mice) | Mediate pathological angiogenesis during hyperinsulinemia and insulin resistance | 525 |
| IRS-1 rs956115 genotypes | (Human) | IRS-1 CG/GG genotype are at higher risk of major adverse cardiovascular events | 526 |
| Therapeutic effect | |||
| Amlexanox inhibition of TBK1/IKKe | Serum (human) | Lowering HBA1c, fructosamine, ameliorates metabolic dysfunctions | 527 |
| Loganin inhibition of JNK-IRS-1/Akt/GSK3β | Peripheral nerve (rats), SH-SY5Y cell (human) | Inhibiting oxidative stress-provoked inflammation, improved Nerve pain behaviors | 528 |
| SGLT-2i inhibition of JunD/PPAR-γ, IRS-1, IRS2 | Endocardiomyocytes (human) | Inhibiting JunD/PPAR-γ overexpression and lipid accumulation, ameliorate diabetic cardiomyopathy | 529 |
C1P ceramide-1-phosphate, IRS insulin receptor substrate, PTP1B protein tyrosine phosphatase, non-receptor type 1, SMPDL3b sphingomyelin phosphodiesterase acid-like 3b, Cav-1 caveolin-1, IGF1 insulin-like growth factor 1, SRF serum response factor, SDF-1 stromal cell-derived factor-1, CXCR4 CXC receptor 4, CD31 endothelial cell adhesion molecule-1, eNOS endothelial nitric oxide synthase, ECs endothelial cells, ceRNAs competing endogenous RNAs, Akt protein kinase B, KLF4 Krüppel-like factor 4, QKI-7 quaking-7, EPDR1 ependymin-related protein-1, TBK1 TANK binding kinase 1, IKKe IkappaB kinase, HBA1c glycated hemoglobin, JNK c-Jun N-terminal kinase, GSK3β glycogen synthase kinase-3β, JunD jund proto-oncogene subunit