Summary
Using I131 VLDL selectively labelled in the B-apoprotein and I125 LDL injected simultaneously into the patient we have derived some quantitative measures of VLDL and LDL metabolism in man. The effects of insulin resistance, associated with idiopathic hypertriglyceridaemia, adult onset diabetes and diabetic lipodystrophy on the metabolic behaviour of these molecules were also assessed. In the normal subjects 72–83% of the total daily plasma VLDL B-apoprotein flux was metabolised via a pathway which involved its ultimate conversion to plasma LDL, while 21–28% was degraded without such conversion. The amount of B-apoprotein metabolised by either of these routes was proportionate to the flux rate and the two pathways accounted for the total VLDL B-apoprotein removed from the plasma. In patients with idiopathic hypertriglyceridaemia and in the adult onset diabetics the total plasma VLDL B-apoprotein flux was higher than normal, indicating increased production of this apoprotein. On the other hand, the flux rate of plasma VLDL B-apoprotein in the patients with diabetic lipodystrophy was normal, suggesting that the increase in the circulating mass of these molecules was due to impaired clearance. In all the patients, however, the fractions of the total flux either converted to LDL or degraded were lower than normal, suggesting that insulin resistance limited the removal of this apoprotein by these pathways. The results also indicate that a fraction of the total VLDL removed from the plasma has been retained in an extravascular compartment, possibly representing VLDL molecules trapped in the vascular structures. In the control and the insulin resistant subjects the quantity of LDL apoprotein catabolised per day agreed closely with the amount derived from VLDL B-apoprotein conversion, suggesting that VLDL-B-apoprotein serves as the main source of LDL apoprotein. In patients with idiopathic hypertriglyceridaemia and in adult onset diabetics the absolute turnover rate of plasma LDL apoprotein was higher than normal, while in the lipodystrophic patients it was reduced. It is suggested that the increase in LDL turnover seen in the former groups could be an additive factor in the deposition of lipid rich material in arterial walls.
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Nikkila, E. A., Ogala, K.: Role of hepatic L-alpha-glycerophosphate and triglyceride synthesis in production of fatty liver by ethanol. Proc. Soc. exp. Biol. (N.Y.)113, 814–817 (1963)
Stout, R. W., Vallance Owen, J.: Insulin and atheroma. Lancet1969 I, 1078–1080
Peters, N., Hales, C. N.: Plasma insulin concentration after myocardial infarction. Lancet1965 I, 1144–1145
Welborn, T. A., Breckenridge, A., Rubenstein, A. H., Dollery, C. T., Fraser, T. R.: Serum insulin in essential hypertension and in peripheral vascular disease. Lancet1966 I, 1336–1337
Olefsky, J. M., Farquhar, J. W., Reaven, G. M.: Reappraisal of the role of insulin in hypertriglyceridaemia. Amer. J. Med.57, 551–560 (1974)
Kissebah, A. H., Alfarsi, S., Adams, P. W., Wynn, V.: Role of insulin resistance in adipose tissue and liver in the pathogenesis of endogenous hypertriglyceridaemia in man. Diabetologia (in press)
Bierman, E. L., Stein, O., Stein, Y.: Lipoprotein uptake and metabolism by rat aortic smooth muscle cells in tissue culture. Circulat. Res.35, 136–150 (1974)
Ross, R.: Growth of smooth muscle in culture and formation of elastic fibres. J. Cell Biol.50, 172–186 (1971)
Ross, R., Glomset, J. A.: Atherosclerosis and arterial smooth muscle cell: Proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science180, 1332–1338 (1973)
Bilheimer, D. W., Eisenberg, S., Levy, R. I.: The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim. biophys. Acta. (Amst.)260, 212–221 (1972)
Eisenberg, S., Bilheimer, D. W., Levy, R. I.: The metabolism of very low density lipoprotein proteins. II. Studies on the transfer of apoproteins between plasma lipoproteins. Biochim. biophys. Acta. (Amst.)280, 94–104 (1972)
Weinhouse, S., Hirsch, E. F.: Chemistry of atherosclerosis. I. Lipid and calcium content of the intima and of the media of the aorta with and without atherosclerosis. Arch. Path.29, 31–40 (1940)
Bierman, E. L., Albers, J. J.: Lipoprotein uptake by cultured human arterial smooth muscle cells. Biochim. biophys. Acta. (Amst.)388, 198–202 (1975)
Hatch, F. T., Lees, R. S.: Practical methods for plasma lipoprotein analysis. In: Advances in lipid research (eds. R. Paoletti, D. Kritchevsky),6, p. 16. New York — London: Academic Press 1968
Levy, R. L., Lees, R. S., Frederickson, D. S.: The nature of pre-beta (very low density) lipoproteins. J. clin. Invest.45, 63–77 (1966)
Brown, V. W., Levy, R. I., Frederickson, D. S.: Studies of protein in human plasma very low density lipoproteins. J. biol. Chem.244, 5687–5693 (1969)
McFarlane, A. S.: Efficient trace-labelling of proteins with iodine. Nature182, 53 (1958)
Kane, J. P.: A rapid electrophoretic technique for identification of sub-unit species of apoproteins in serum lipoproteins. Analyt. Biochem.53, 350–356 (1973)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with folinphenol reagent. J. biol. Chem.193, 265–275 (1951)
Scott, P. J., White, B. M., Winterbourn, C. C., Hurley, P. J.: Low density lipoprotein peptide metabolism in nephrotic syndrome: A comparison with patterns observed in other syndromes characterised by hyperlipoproteinaemia. Aust. Ann. Med.1, 1–15 (1970)
Zilversmit, D. B.: The design and analysis of isotope experiments. Amer. J. Med.19, 832–848 (1960)
Hart, H., Spencer, H.: Rate of initial entry of Ca47 and Sr85 from the intestine into the vascular space. Proc. Soc. exp. Biol. (N.Y.)126, 365–371 (1967)
Sigurdsson, G., Nicoll, A., Lewis, B.: Interconversion of lipoproteins: Is all low density lipoprotein-peptide derived from very low density lipoprotein peptide. Clin. Sci. Mol. Med.48, 149 (1975)
Matthews, C. M. E.: The theory of tracer experiments with I131 labelled plasma proteins. Phys. in Med. Biol.2, 36–45 (1957)
Eisenberg, S., Rachmilewitz, D.: Metabolism of rat plasma very low density lipoprotein. I. Fate in circulation of the whole lipoprotein. Biochim. biophys. Acta. (Amst.)326, 378–390 (1973).
Eisenberg, S., Rachmilewitz, D.: Metabolism of rat plasma very low density lipoprotein. II. Fate in circulation of apoprotein sub-units. Biochim. biophys. Acta. (Amst.)326, 391–405 (1973)
Steinberg, D. S.: Degradation of LDL by peripheral tissues in vivo and in vitro. In: Familial Hypercholesterolaemia Workshop held at the Hammersmith Hospital, London. Sept. 8–10, 1975, p. 84–93
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Kissebah, A.H., Alfarsi, S., Adams, P.W. et al. The metabolic fate of plasma lipoproteins in normal subjects and in patients with insulin resistance and endogenous hypertriglyceridaemia. Diabetologia 12, 501–509 (1976). https://doi.org/10.1007/BF01219515
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DOI: https://doi.org/10.1007/BF01219515