Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myocytes for lipoprotein triglyceride oxidation. In human obesity, an insulin-resistant state, SMLPL levels measured in the fasted state are either decreased or unchanged as compared with levels in normal-weight controls. However, insulin/glucose infusion increases SMLPL activity in obese individuals, whereas in normal-weight subjects the activity is decreased. One of the goals of this study was to determine the impact of obesity with concomitant non-insulin-dependent diabetes mellitus (NIDDM) on fasting SMLPL and on the change in SMLPL activity (delta MLPL) in response to an insulin/glucose infusion. Because NIDDM is often a more insulin-resistant state, it was hypothesized that SMLPL activity would be further increased by insulin/glucose in subjects who were obese and had NIDDM. Measurements of SMLPL were made from biopsies of vastus lateralis skeletal muscle taken before and after a 6-hour insulin/glucose infusion in the setting of a euglycemic clamp. Thirteen nondiabetic obese women (OBC) and six nondiabetic normal-weight women (NWC) were used as control subjects. SMLPL levels measured in the fasted state were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calculation of the mean glucose infusion rate (GIR) required to sustain euglycemia over the last 60 minutes of the infusion. For all three groups combined, representing a continuum of insulin sensitivity, there was a positive correlation between GIR and fasting SMLPL. As described earlier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after insulin/glucose.(ABSTRACT TRUNCATED AT 250 WORDS)