Peran biologis Uncoupling Protein 2 (UCP2) pada obesitas dan diabetes mellitus tipe 2 (DMT2)

Abstract

Obesity is a symptom or disorder determined by the interaction of several environmental and genetic factors. It is a result of imbalance between energy intake and expenditure. It is also suggested that obesity increases the risk of Type 2 Diabetes Mellitus (T2DM). It has been reported that uncoupling protein 2 (UCP2) may influence the susceptibility to obesity and T2DM. The aims of this literature study is to elucidate the biological role of UCP2 in obesity and T2DM. UCP2 is a transporter of the mitochondrial inner membrane that can uncouple proton production from mitochondrial respiration, thereby dissipating energy as heat and affecting energy expenditure. UCP2 acts as a proton carrier activated by free fatty acids. Obesity and fasting can elevate plasma fatty acids. High plasma fatty acid levels can increase UCP2 mRNA levels suggesting the role of these protein in the metabolic adaptation to obesity and fasting. Moreover, UCP2 plays a role as a negative regulator of insulin secretion. In pancreatic beta cells the ratio of ATP/ADP is key signal for insulin release. Therefore, increase UCP2 expression, as seen in the pancreatic beta cell, might cause a decrease in intracellular ATP and results in the impairment of insulin secretion, which causes diabetes. Ala55Val allele of UCP2 gene, as single nucleotide polymorphisms (SNPs) may influence the susceptibility to obesity and T2DM. However, the association of this allele to obesity and diabetes is different in various populations