Genetic Variance in Uncoupling Protein 2 in Relation to Obesity, Type 2 Diabetes, and Related Metabolic Traits: Focus on the Functional −866G>A Promoter Variant (rs659366)

Figure 1

Mechanism by which UCP2 activation may lead to obesity and type diabetes. UCP2 upregulation by nutrients (glucose, lipids, fatty acids, glutamine (protein-rich diet)) increases UCP2 mRNA transcription or translation. UCP2 activity is increased by superoxide radicals. Increased UCP2 amount or activity causes β-cell dysfunction [29] and may contribute to decreased metabolic efficiency by decreasing ATP-generation. UCP2 activation decreases oxidative stress and may therefore decrease aging [30], cancer progression [31], and inflammation [32]. Decreased ROS levels may also protect β-cell [33]. Decreased ATP-generation by UCP2 upregulation may cause less efficient metabolism and protect against obesity, which will decrease demand for insulin secretion by the β-cell.