The objective of this project is to investigate the role of fat cell metabolism in the pathogenesis of insulin resistance and non-insulin- dependent diabetes mellitus. Two hypotheses form the basis for the proposed series of experiments: 1) it is hypothesized that direct intervention to alter fat distribution from the truncal obesity which typifies the patient with the insulin resistance syndrome will ameliorate the characteristic metabolic abnormalities, to a greater extent than if an equivalent weight reduction is achieved by dietary means; 2) protein tyrosine phosphatases (PTPs) are enzymes known to be functionally important in the regulation of insulin signaling. It is hypothesized by this study that specific PTPs are present in adipose tissue, playing a role in its specialized functions, and in the pathogenesis of NIDDM. Human fat cells will be screened for the expression of PTP's and in order to deduce the sequence, substrate specificity, cellular localization and functional importance of the putative enzyme(s) in normal subjects and individuals with NIDDM.