Two recently described proteins in the mitochondrial uncoupling protein (UCP) family, UCP-2 and UCP-3, have been linked to phenotypes of obesity and NIDDM. We determined the mRNA levels of UCP-2 and UCP-3 in skeletal muscle of NIDDM patients and of healthy control subjects. No difference in the mRNA levels or in the protein expression of UCP-2 was observed between the two groups. In contrast, mRNA levels of UCP-3 were significantly reduced in skeletal muscle of NIDDM patients compared with control subjects. In the NIDDM patients, a positive correlation between UCP-3 expression and whole-body insulin-mediated glucose utilization rate was also noted. These results suggest that UCP-3 regulation may be altered in states of insulin resistance. [ABSTRACT FROM AUTHOR]