Advertisement

Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Metabolism of very low- and low-density lipoproteins isolated from normolipidaemic Type 2 (non-insulin-dependent) diabetic patients by human monocyte-derived macrophages

  • 68 Accesses

  • 27 Citations

Summary

The very low- and low-density lipoprotein fractions were isolated from 16 normolipidaemic Type 2 (non-insulin-dependent) diabetic patients in good to fair glycaemic control and from corresponding age-, sex-, and race-matched, non-diabetic control subjects. Rates of cholesteryl ester synthesis averaged 268±31 vs 289±40 pmol 14C-cholesteryl oleate·-mg cell protein−1·20 h−1 for very low- and 506±34 vs 556±51 pmol 14C-cholesteryl oleate·mg cell protein−1·20 h−1 for low-density lipoproteins isolated from the Type 2 diabetic patients and control subjects, respectively, when they were incubated with human macrophages. A group of approximately one-third of the patients was selected for separate analyses because very low-density lipoproteins isolated from these patients did stimulate more cholesteryl ester synthesis when incubated with macrophages. There were no significant differences in the lipid composition of the lipoproteins isolated from the three groups of subjects. The relative proportion of apoprotein C to apoprotein E was significantly decreased (p<0.002) in the very low-density lipoproteins from diabetic patients and was further decreased in samples from these selected diabetic patients. The apoprotein C-I content of very low-density lipoproteins isolated from diabetic patients was increased compared to control subjects and was further increased in samples from the selected diabetic patients (p<0.02). There were no significant differences in the proportions of apoproteins C-III-0, C-III-1, or C-III-2 among the three groups. These studies suggest that in normolipidaemic Type 2 diabetic patients, the apoprotein composition of VLDL is abnormal and this may alter VLDL macrophage interactions and thus contribute to the increased prevalence of atherosclerosis in diabetic patients.

References

  1. 1.

    West KM (1982) Hyperglycemia as a cause of long-term complications. In: Keen H, Jarrett RJ (eds) Complications of diabetes. Edward Arnold, London, pp 13–18

  2. 2.

    Garcia MJ, McNamara PM, Gordon T, Kannel WB (1974) Morbidity and mortality in diabetics in the Framingham population. Diabetes 23: 105–111

  3. 3.

    Chait A, Bierman EL, Brunzell JD (1985) Diabetic macroangiopathy. In: Albert KGMM, Krall LP (eds) The diabetes annual/1. Elsevier, New York, pp 323–348

  4. 4.

    Lopes-Virella MF, Sherer GK, Lees AM, Wohltmann H, Mayfield R, Sagel J, LeRoy EC, Colwell JA (1982) Surface binding, internalization and degradation by cultured human fibroblasts of low density lipoproteins isolated from Type 1 (insulin-dependent) diabetic patients: changes with metabolic control. Diabetologia 22: 430–436

  5. 5.

    Kraemer FB, Chen Y-DI, Cheung RMC, Reaven GM (1982) Are the binding and degradation of low density lipoprotein altered in Type 2 (non-insulin-dependent) diabetes mellitus? Diabetologia 23: 28–33

  6. 6.

    Hiramatsu K, Bierman EL, Chait A (1985) Metabolism of low-density lipoprotein from patients with diabetic hypertriglyceridemia by cultured human skin fibroblasts. Diabetes 34: 8–14

  7. 7.

    Gonen B, Baenziger J, Schonfeld G, Jacobson D, Farrar P (1981) Nonenzymatic glycosylation of low-density lipoprotein in vitro. Diabetes 30: 875–878

  8. 8.

    Witztum JL, Mahoney EM, Branks MJ, Fisher M, Elam R, Steinberg D (1982) Nonenzymatic glucosylation of low-density lipoprotein alters its biologic activity. Diabetes 31: 283–291

  9. 9.

    Sasaki J, Cottam GL (1982) Glycosylation of LDL decreases its ability to interact with high affinity receptors of human fibroblasts in vitro and decreases its clearance from rabbit plasma in vivo. Biochim Biophys Acta 713: 199–207

  10. 10.

    Schleicher E, Olgemoller B, Schon J, Durst T, Wieland OH (1985) Limited nonenzymatic glucosylation of low-density lipoprotein does not alter its catabolism in tissue culture. Biochim Biophys Acta 846: 226–233

  11. 11.

    Steinbrecher UP, Witztum JL (1984) Glucosylation of low-density lipoprotein to an extent comparable to that seen in diabetes slows their catabolism. Diabetes 33: 130–134

  12. 12.

    Lorenzi M, Cagliero E, Markey B, Henriksen T, Witztum JL, Sampietro T (1984) Interaction of human endothelial cells with elevated glucose concentrations and native and glycosylated low density lipoproteins. Diabetologia 26: 218–222

  13. 13.

    Lamamoto M, Ranganathan S, Kottke BA (1986) Metabolism of glycosylated very low-density lipoprotein in human skin fibroblasts. Biochim Biophys Acta 875: 410–413

  14. 14.

    Lopes-Virella MF, Klein RL, Lyons TJ, Stevenson HC, Witztum JL (1988) Glycation of low-density lipoproteins enhances cholesteryl ester synthesis in human monocyte macrophages. Diabetes 37: 550–557

  15. 15.

    Lyons TJ, Klein RL, Baynes JW, Stevenson HC, Lopes-Virella MF (1987) Stimulation of cholesteryl ester synthesis in human monocyte-derived macrophages by low-density lipoproteins from Type 1 (insulin-dependent) diabetic subjects: the influence of non-enzymatic glycosylation of low-density lipoproteins. Diabetologia 30: 916–923

  16. 16.

    Klein RL, Lyons TJ, Lopes-Virella MF (1989) Interaction of VLDL isolated from Type 1 (insulin-dependent) diabetic subjects with human monocyte derived macrophages. Metabolism 38: 1108–1114

  17. 17.

    Kraemer FB, Chen Y-DI, Lopez RD, Reaven GM (1985) Effects of non-insulin-dependent diabetes mellitus on the uptake of very low density lipoproteins by thioglycolate-elicited mouse peritoneal macrophages. J Clin Endocrinol Metab 61: 335–342

  18. 18.

    National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28: 1039–1057

  19. 19.

    Stevenson HC, Beman JA, Oldham RK (1983) Design of a cancer immunology cytapheresis unit. Plasma Therapy 4: 57–63

  20. 20.

    Stevenson HC (1985) Separation of mononuclear leukocyte subsets by countercurrent centrifugation elutriation. In: Gosabato G, Langone T, von Vunakis H (eds) Methods in enzymology: immunochemical techniques, part G. Academic Press, New York, pp 242–249

  21. 21.

    Stevenson HC, Katz P, Wright DG, Contreras TJ, Jemionek JF, Hartwig VM, Flor WJ, Fauci AS (1981) Human blood monocytes: characterization of the negatively selected human monocyte and their suspension cell culture derivatives. Scand J Immunol 14: 243–256

  22. 22.

    Folch J, Lees M, Stanley GHS (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509

  23. 23.

    Ishikawa TT, McGee Y, Morrison JA, Glueck CJ (1974) Quantitative analyses of cholesterol in 5 to 20 μl of plasma. J Lipid Res 15: 286–291

  24. 24.

    Manual of Lipid Operations (1974) Lipid Research Clinics Program, Vol.1. Lipid and lipoprotein analysis, Dept. of Health, Education and Welfare, Publ. No. (NIH) 75-628, pp 9–37

  25. 25.

    Bartlett GR (1959) Phosphorus assay in column chromatography. J Biol Chem 234: 466–468

  26. 26.

    Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 87: 206–211

  27. 27.

    Lopes-Virella MF, Virella G, Evans G, Malenkas SB, Colwell JA (1980) Immunonephelometric assay of human apolipoprotein A-I. Clin Chem 26: 1205–1208

  28. 28.

    Warnick GR, Mayfield C, Albers JJ, Hazzard WR (1979) Gel isolectric focusing method for specific diagnosis of familial hyperlipoproteinemia Type 3. Clin Chem 25: 279–284

  29. 29.

    Reisner AH, Nemes P, Bucholtz C (1975) The use of Coomassie brilliant blue G-250 perchloric acid solution for staining in electrophoresis and isolectric focusing on polyacrylamide gels. Anal Biochem 64: 509–516

  30. 30.

    Holbrook IB, Leaver AG (1976) A procedure to increase the sensitivity of staining by Coomassie brilliant blue G-250 perchloric acid solution. Anal Biochem 75: 634–636

  31. 31.

    Catapano AL (1980) The distribution of apo C-II and apo C-III in very low density lipoproteins of normal and type IV subjects. Atherosclerosis 35: 419–424

  32. 32.

    Kashyap ML, Hynd BA, Robinson K, Gartside PS (1981) Abnormal preponderance of sialylated apolipoprotein C-II in triglyceride-rich lipoproteins in type V hyperlipoproteinemia. Metabolism 30: 111–118

  33. 33.

    Lyons TJ, Baynes JW, Patrick JS, Colwell JA, Lopes-Virella MF (1986) Glycosylation of low density lipoprotein in patients with Type 1 (insulin-dependent) diabetes: correlations with other parameters of glycaemic control. Diabetologia 29: 685–689

  34. 34.

    Kadish AH, Little RL, Steinberg JC (1986) A new and rapid method for the determination of glucose by measurement of rate of oxygen consumption. Clin Chem 14: 116–131

  35. 35.

    Spicer KN, Allen RC, Buse MG (1978) A simplified assay of hemoglobin A1C in diabetic patients using isoelectric focusing and quantitative microdensitometry. Diabetes 27: 384–388

  36. 36.

    Lopes-Virella MF, Stone P, Ellis S, Colwell JA (1977) Cholesterol determination in high density lipoproteins separated by three different methods. Clin Chem 23: 882–884

  37. 37.

    Weisweiler P, Schwandt P (1987) Type 1 (insulin-dependent) versus Type 2 (non-insulin-dependent) diabetes mellitus: characterization of serum lipoprotein alterations. Eur J Clin Invest 17: 87–91

  38. 38.

    Weisweiler P, Drosner M, Schwandt P (1982) Dietary effects on very low-density lipoproteins in Type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 23: 101–103

  39. 39.

    Kasama T, Yoshino G, Iwatani I, Iwai M, Hatanaka H, Kazumi T, Oimomi M, Baba S (1987) Increased cholesterol concentration in intermediate density lipoprotein fraction of normolipidemic non-insulin-dependent diabetics. Atherosclerosis 63: 263–266

  40. 40.

    Taskinen MR, Beltz WF, Harper I, Fields RM, Schonfeld G, Grundy SM, Howard BV (1986) The effects of non-insulin-dependent diabetes mellitus on VLDL triglyceride and VLDL apo B metabolism: studies before and after sulfonylurea therapy. Diabetes 35: 1268–1277

  41. 41.

    Pagnan A, Padovan D, Guarini P, Teodoro N, Zanetti G (1980) Serum lipids and apoprotein composition (%) of the very low density lipoprotein (VLDL) fraction in two groups of diabetic patients: effects of oral as compared to insulin therapy. Acta Diabetol Lat 17: 225–228

  42. 42.

    Gabor J, Spain M, Kalant N (1980) Composition of serum very-low-density and high-density lipoproteins in diabetes. Clin Chem 2: 1261–1265

  43. 43.

    Stalenhoef AFH, Demacker PNM, Lutterman JA, van't Laar A (1982) Apolipoprotein C in Type 2 (non-insulin-dependent) diabetic patients with hypertriglyceridaemia. Diabetologia 22: 489–491

  44. 44.

    Shoukry MI (1986) Apo C-III levels in Type IV hyperlipoproteinemia associated with non-insulin dependent diabetes. Indian J Med Res 84: 297–300

  45. 45.

    Pan X-R, Cheung MC, Walden CE, Hu S-X, Bierman EL, Albers JJ (1986) Abnormal composition of apoproteins C-I, C-II, and C-III in plasma and very-low-density lipoproteins of non-insulin-dependent diabetic Chinese. Clin Chem 32: 1914–1920

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Klein, R.L., Lyons, T.J. & Lopes-Virella, M.F. Metabolism of very low- and low-density lipoproteins isolated from normolipidaemic Type 2 (non-insulin-dependent) diabetic patients by human monocyte-derived macrophages. Diabetologia 33, 299–305 (1990). https://doi.org/10.1007/BF00403324

Download citation

Key words

  • Type 2 (non-insulin-dependent) diabetes mellitus
  • VLDL metabolism
  • LDL metabolism
  • human macrophages