We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity.
Inactivation of the Ucp2 gene, which is expressed in the pancreatic beta-cells, resulted in increased islet ATP, increased serum insulin levels, and suppression of the diabetes of the ob/ob mouse genotype.
The presence of a mixed genetic background in most published studies of UCP2 or UCP3 gene-ablated mice also means that data concerning marked differences in diabetes propensity, infection sensitivity and production of reactive oxygen species may require confirmation in backcrossed mice.
Polymorphisms in the mitochondrial membrane transporter gene UCP2 are capable of affecting energy metabolism, body weight regulation, and possibly preventing the buildup of reactive oxygen species, all factors that could contribute to neural tube defect risk through maternal obesity and diabetes.
To test this hypothesis we searched for association between the A-->G (-3862) variant in UCP1, the insertion/deletion (I/D) polymorphism in exon 8 in UCP2, and the C-->T (-55) polymorphism in UCP3 and diabetic nephropathy in 218 diabetic patients with normal urinary albumin excretion rate (AER), 216 with micro- or macroalbuminuria, and in 106 control subjects without a family history of diabetes.
We also tested for an effect of the P12A variant of the peroxisomal proliferator-activated receptor-gamma 2 (PPAR gamma 2) gene on diabetes risk given by the UCP2 SNP.
Our data suggest that agents increasing UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes and hypertension.
UCP-2 can possibly modify atherosclerotic processes initiated in vascular cells and agents that increase UCP-2 expression in vascular cells may help prevent the development and progression of atherosclerosis in patients with diabetes or hypertension.
These findings suggest a role of UCP2-UCP3 gene cluster haplotypes in diabetes; in particular, the effects of the high-risk haplotypes were more apparent in overweight Caucasian women.
This review summarizes data supporting the roles of UCP2 and UCP3 in energy dissipation, as well as the genetic variety association with fat metabolism, obesity and diabetes in humans.
A variant in the promoter of the human uncoupling protein 2 (UCP2) gene, the G-866A polymorphism, has been associated with future risk of coronary heart disease events, in those devoid of traditional risk factors and in those suffering from diabetes.
We explored the associations of three variants in the uncoupling protein 2 (UCP2) gene, one variant in the UCP2-UCP3 intergenic region and five variants in the uncoupling protein 3 (UCP3) gene with obesity and diabetes related traits in subjects with impaired glucose tolerance participating in Finnish Diabetes Prevention Study.
UCP2 -866G>A (rs659366) has been implicated in cardiometabolic disease and represents a novel candidate gene for beta-blocker response, particularly among patients with diabetes.