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...

Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 µg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [14 C]-acetate. Saquinavir increased the lipolysis.Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulinstimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs.

No abstract

Background: Prognosis of Triple-Negative Breast Cancer (TNBC) and non-TNBC has been evaluated predominantly in smaller subset of patients, and pooled analyses include various subsets of institutional standards. The West German Breast Center includes more than 200 certified breast units covering approx. 65 % of all breast cancer cases in the country. Material and Methods: We included all primary breast cancer cases of the last 3 years whenever patients received any kind of neoadjuvant or adjuvant chemotherapy in all certified breast units affiliated to the West German Breast Center. Data was submitted in a computer-based registry, where standardized data is prospectively collected. Data monitoring and benchmarking is held 6-monthly which guarantees a high standard of performance. Results: 34 675 non-TNBC patients achieved a DFS of 92,4 % at 2 years and 81,2 % at 3 years whereas out of 3728 TNBC-patients only 79 % were disease-free at 2 years and 57,4 % at 3 years. With regards to overall survival 97,3 % of non-TNBC patients were alive at 2 years and 92,2 % at 3 years, whereas 89,3 % TNBC-patients were alive at 2 years and 82,9 % at 3 years. Conclusion: In this large registry of certified breast units from the West German Breast Center we could underline the significant differences of prognosis as to DFS and OS between the non-TNBC and TNBC-subgroup of patients, displaying survival rates with modern 3rd generation chemotherapy, surgical treatment and radiotherapy in a controlled setting with prospectively collected data. To is, to our best knowledge, one of the largest data sets ever exploring the differences in prognosis between TNBC and non-TNBC-patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-14.

No abstract