Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase

Abstract

Lipoprotein lipase plays a key role in the catabolism of triglyceride(TG)-rich lipoproteins [1], and it is generally accepted that the activity of this enzyme is decreased in insulin-deficient states [2][3][4]. While alterations in LPL have long been suspected in insulin resistance [1,5], the situation concerning the relationship between LPL and insulin-mediated glucose disposal is more complicated. Patients with non-insulin-dependent diabetes mellitus are generally assumed to be insulin resistant [6,7], and there is evidence that LPL activity is decreased in these subjects [8,9]. However, this conclusion is confounded by not knowing whether the changes noted are due to the insulin resistance, the decrease in plasma insulin concentration or the ambient hyperglycaemia that is also present in these individuals. One approach to evaluating the effect of insulin resistance per se on LPL activity, is to study normal glucose tolerant individuals. Results of recent studies have shown that LPL activity was reduced in post-heparin (PH) plasma [10,11], skeletal muscle [12,13] and adipose tissue [14,15] of insulin resistant individuals. To our knowledge, however, adipose tissue LPL activity, Diabetologia (1997) 40: 850-858 Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase Summary The relationship between insulin-mediated glucose disposal and fasting insulin and triglyceride (TG) concentrations, plasma post-heparin lipoprotein lipase (PH-LPL) activity and mass, and adipose tissue LPL activity, mass, and mRNA content was defined in 19 non-diabetic men. Insulin-mediated glucose uptake [as assessed by determining the steady-state plasma glucose (SSPG) concentration during a continuous infusion of somatostatin, insulin, and glucose] was significantly correlated with fasting TG concentration (r = 0.54, p < 0.02), plasma PH-LPL activity (r = -0.52, p < 0.03) and mass (r = -0.49, p < 0.03), and adipose tissue LPL mRNA content (r = -0.68, p < 0.001). Comparable relationships were also seen when fasting insulin concentration was substituted for SSPG. Although adipose tissue LPL and mass correlated with each other (r = 0.76, p < 0.001) in a fasting state, they were not related to any other variable measured. Using in vivo and molecular biology techniques, these data demonstrate that the more insulin resistant an individual, the lower the level of plasma PH-LPL activity and mass, and the higher the plasma TG concentration. Since lower concentrations of adipose tissue mRNA were also directly correlated with plasma PH-LPL mass (r = 0.57, p < 0.01), and inversely with plasma TG concentration (r = -0.68, p < 0.001) as well as SSPG (r = -0.68, p < 0.001), it can be postulated that the relationship between insulin resistance and LPL activity and plasma TG concentration is associated with the inability of insulin to stimulate the transcription or to increase the intracellular mRNA stability of adipose tissue LPL in insulin resistant individuals. [Diabetologia (1997) 40: 85...

Triglyceride-Based Screening Tests Fail to Recognize Cardiometabolic Disease in African Immigrant and African-American Men

“…However, it is known that the activity of lipoprotein lipase (LPL), the enzyme that clears TG from the circulation, is higher in blacks than whites. 43 In addition, even though insulin resistance should impair LPL activity, 44 we have previously shown that LPL activity does not decline in insulin-resistant African Americans. 45 …”

Functional significance of lipoprotein lipase HindIII polymorphism associated with the risk of coronary artery disease

“…For example, it has been shown that LPL mRNA increase significantly in brown adipose tissue after insulin injection to fasting rats [46]. On the other hand, LPL activity is reduced under insulin resistance state because the ability of insulin to up-regulate LPL gene is impaired in insulin resistant individuals, leading to hypertriglyceridemia [47]. It is conceivable that insulin differentially affects the allele-specific effect of the HindIII polymorphism in individuals with different state of insulin sensitivity.…”

Effect of a moderate weight loss on adipose tissue lipoprotein lipase activity and expression: existence of sexual variation and regional differences

“…Even though we did not measure the lipoprotein lipase mass, it is likely that weight loss induced a decrease AT-LPL activity of women through postranslational mechanisms, as already documented. 9,11,46 Finally, it is well known that a substantial part of HDL is derived from surface constituents of chylomicrons and VLDL during breakdown of their triglycerides by lipoprotein lipase. 47,48 In this regard, Magill et al 49 have already observed that a high gluteal AT-LPL activity increased the fractional rate of catabolism of VLDL, which, in turn, raised HDL-C concentrations.…”