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Overall, these studies show that oxidative and glucose stresses induced TXNIP levels at both the transcriptional and translational levels (Figure 5B) and that IGF-1 indirectly regulates cellular TXNIP, protecting the cells from apoptosis (Figure 5C) [79]

doi: 10.36660/abc.20200044

Hyperpigmentation is often more pronounced on the limbs, primarily on the dorsum of the hands and feet, in flexural areas, and occasionally on the nails, tongue, and oral mucous membranes.3 Since hyperpigmentation is a nonspecific symptom, a broad range of differential diagnoses should be considered in such cases: diabetes mellitus, Addison disease, Cushing syndrome, post-inflammatory lesions, amyloidosis, melanosis of the skin, heavy metal deposition, thyroid disease, tumors, drug reactions, and porphyria cutanea tarda, among others.4 The pathophysiology of hyperpigmentation is still a matter of debate

Furthermore, smoking induces vascular vasoconstriction, sinusoidal endothelial dysfunction, and smooth muscle proliferation, leading to hypoxia, capillarization of sinusoids, and further activation of HSCs [18]