CHANGE IN SKELETAL-MUSCLE LIPOPROTEIN-LIPASE ACTIVITY IN RESPONSE TO INSULIN GLUCOSE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myo cytes for lipoprotein triglyceride oxidation. In human obesity, an ins ulin-resistant state, SMLPL levels measured in the fasted state are ei ther decreased or unchanged as compared with levels in normal-weight c ontrols. 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 (N IDDM) 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 ob ese and had NIDDM. Measurements of SMLPL were made from biopsies of va stus lateralis skeletal muscle taken before and after a 6-hour insulin /glucose infusion in tile setting of a euglycemic clamp. Thirteen nond iabetic obese women (OBC) and six nondiabetic normal-weight women (NWC ) were used as control subjects. SMLPL levels measured in the fasted s tate were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calcu lation of the mean glucose infusion rate (GIR) required to sustain eug lycemia 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 ear lier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after i nsulin/glucose. In contrast, SMLPL activity did not change after insul in/glucose infusion in obese NIDDM subjects. Overall, these data indic ate that although insulin action seems to be important in determining the level of SMLPL activity measured in the fasted state in human subj ects, it is not the major contributor to the change in SMLPL activity that occurs in response to an insulin/glucose infusion. Copyright (C) 1995 by W.B. Saunders Company