Hormonal
Inhibition of TXNIP expression or activity improves insulin sensitivity, protects pancreatic beta-cells from apoptosis, and ameliorates metabolic abnormalities in type 2 diabetes and obesity.
Targeting TXNIP is a promising therapeutic strategy for managing Type 2 Diabetes and obesity. Drugs like Metformin, GLP-1 agonists, and potentially repurposed drugs like Verapamil work partly by lowering TXNIP levels. This improves insulin sensitivity and protects pancreatic cells. However, because TXNIP helps maintain blood sugar during fasting, inhibitors must be carefully dosed to avoid hypoglycemia and potential long-term cancer risks associated with its loss.
Overexpression of TXNIP in animal models has been shown to induce apoptosis of pancreatic β-cells, reduce insulin sensitivity in peripheral tissues like skeletal muscle and adipose, and decrease energy expenditure. On the contrary, TXNIP deficient animals are protected from diet induced insulin resistance and type 2 diabetes.
Why this rating
Strong evidence from animal models and human cell lines; human clinical data is emerging (Phase 2 trials).
Source
TXNIP in Metabolic Regulation: Physiological Role and Therapeutic Outlook
Naif Mohammad Alhawiti et al. · Current Drug Targets · 2017
DOI 10.2174/1389450118666170130145514
More from this paper
- Existing anti-diabetic medications, including Metformin, GLP-1 agonists, and Verapamil, exert part of their therapeutic effect by downregulating TXNIP expression.Good
- TXNIP acts as a nutrient sensor in the hypothalamus to regulate energy expenditure and adiposity; its overexpression in Agouti-related protein (AGRP) neurons leads to diet-induced obesity.Good
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