Abstract
The role of the intestine in cholesterol metabolism in human diabetes in unclear, although abnormalities have been demonstrated in cholesterol synthesis and absorption in diabetic animals. This study examines the relationship between fasting and post-prandial apolipoprotein B-48 in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Eight type 2 diabetic patients and ten healthy non-diabetic control subjects were given a high-fat meal (1300 kcal), and the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d<1.006 g/ml) from fasting and post-prandial plasma. Apolipoprotein B-48 and apo B-100 were separated on 4%–15% gradient gels and quantified by densitometric scanning with reference to a purified low-density lipoprotein (LDL) apo B-100 preparation. Diabetic patients had significantly higher concentrations of apo B-48 and apo B-100 in both the fasting (P<0.05) and post-prandial (P<0.001) triglyceride-rich lipoprotein samples compared with non-diabetic subjects. The diabetic patients also exhibited a significantly different post-prandial profile for apo B-48 and apo B-100, with a prolonged increase and a later post-prandial peak, than the non-diabetic subjects (P<0.01). These results suggest that the raised fasting triglyceride-rich lipoproteins, often found in diabetes, are associated with apo B-48 and may be derived from increased intestinal chylomicron production. The post-prandial pattern suggests an abnormality in intestinal production as well as hepatic clearance of apo B-48 in type 2 diabetes.
Similar content being viewed by others
References
Zilversmit DB, Atherogenesis: a post-prandial phenomenon. Circulation 60:473–485, 1979
Syvanne M, Hilden H, Taskinen M-R, Abnormal metabolism of postprandial lipoproteins in patients with non-insulin-dependent diabetes mellitus is not related to coronary artery disease. J Lipid Res 35:15–26, 1994
Eckel RH, Lipoprotein lipase: a multifunctional enzyme relevant to common metabolic diseases. N Engl J Med 320:1060–1068, 1989
O'Meara N, Devery R, Owens D, Collins P, Johnson A, Tomkin GH, Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models. Diabetologia 34:139–143, 1991
Krasinski SD, Cohn JS, Russell RM, Shaefer EJ, Post-prandial plasma vitamin A metabolism in humans: a re-assessment of the use of plasma retinyl ester as a marker for intestinally-derived chylomicrons and their remnants. Metabolism 39:357–365, 1990
Karpe F, Bell M, Bjorkegren J, Hamsten A, Quantification of postprandial triglyceride-rich lipoproteins in healthy men by retinyl ester labelling and simultaneous measurement of apolipoproteins B48 and B100. Arterioscler Thromb Vasc Biol 15:199–207, 1995
Kane JP, Hardman DA, Paulus HE, Heterogeneity of apolipoprotein B: isolation of a new species from human chylomicrons. Proc Natl Acad Sci USA 77:2465–2469, 1980
Edge SB, Hoeg JM, Schneider, Brewer HB Jr, Apolipoprotein B synthesis in humans: liver synthesizes only apolipoprotein B-100. Metabolism 34:726–730, 1985
Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J, A novel form of tissue-specific RNA processing produces apolipoprotein B-48 in the intestine. Cell 50:831–840, 1987
Glickman RM, Rogers M, Glickman JN, Apolipoprotein B synthesis by human liver and intestine in vitro. Proc Natl Acad Sci USA 83:5296–5300, 1986
Dullart RPF, Speelberg B, Schuurman H-J, Milne RW, Havekes LM, Marcel YL et al, Epitopes of apolipoprotein B-100 and apo B-48 in both liver and intestine. J Clin Invest 87:1397–1404, 1986
Hoeg JM, Sviridov DD, Tennyson GE, Demosky SJ Jr, Meng MS, Bojanovski D et al, Both apolipoproteins B-48 and B-100 are synthesized and secreted by the human intestine. J Lipid Res 31:1761–1769, 1990
Kane JP, Apolipoprotein B: structural and metabolic heterogeneity. Annu Rev Physiol 45:637–650, 1983
Feingold KR, Zsigmond G, Lear SK, Moser AH, The effect of food intake on intestinal cholesterol synthesis in rats. Am J Physiol 251:362–369, 1986
Devery R, O'Meara N, Collins P, Johnson A, Scott L, Tomkin GH, A comparative study of the rate-limiting enzymes of cholesterol synthesis, esterification and catabolism in the rat and rabbit. Comp Biochem Physiol 87B:697–702, 1987
O'Meara N, Devery R, Owens D, Collins P, Johnson A, Tomkin GH, Cholesterol metabolism in the Alloxan-induced diabetic rabbits. Diabetes 39:626–633, 1990
Young NL, Lopez DR, McNamara DJ, Contributions of absorbed dietary cholesterol and cholesterol synthesized in small intestine to hypercholesterolemia in diabetic rats. Diabetes 37:1151–1156, 1988
Feingold KR, Zsigmond G, Hughes-Fulford M, Lear SR, Moser AH, The effect of diabetes mellitus on the lymphatic transport of intestinal sterols. Metabolism 34:1105–1109, 1985
Curtin A, Deegan P, Owens D, Collins P, Johnson A, Tomkin GH, Alterations in apolipoprotein B-48 in the postprandial state in non-insulin-dependent diabetes. Diabetologia 37:1259–1264, 1994
Karpe F, Hamsten A, Determination of apolipoproteins B48 and B100 in triglyceride-rich lipoproteins by analytical SDS-PAGE. J Lipid Res 35:1311–1317, 1994
Markwell MAK, Haas SM, Bieber LL, Tolbert NE, A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal Biochem 87:206–210, 1978
Havel RA, Eder HM, Brayden JH, The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34:1345–1353, 1955
Karpe F, Steiner G, Olivecrona T, Carlson LA, Hamsten A, Metabolism of triglyceride-rich lipoproteins during alimentary lipaemia. J Clin Invest 91:748–758, 1993
Martins IJ, Sainsbury AJ, Mamo JCL, Redgrave TG, Lipid and apoprotein B-48 transport in mesenteric lymph and the effect of hyperphagia on the clearance of chylomicron-like emulsions in insulin-deficient rats. Diabetologia 37:238–246, 1994
Krasinski SD, Cohn JS, Shaefer EJ, Russell RM, Postprandial plasma retinyl ester response is greater in older subjects compared with younger subjects. J Clin Invest 85:883–892, 1990
Cohn SJ, McNamara JR, Cohn SD, Ordovas JM, Shaefer EJ, Postprandial plasma lipoprotein changes in human subjects of different ages. J Lipid Res 29:469–479, 1988
Horowitz, Frazer R, Disordered gastric motor function in diabetes mellitus. Diabetologia 37:543–551, 1994
Taskinen M-R, Kuusi T, Helve E, Nikkila EA, Yki-Jarvinen H, Insulin induces antiatherogenic changes of serum lipoproteins in non-insulin-dependent diabetes. Arteriosclerosis 8:168–177, 1988
Zimmet PZ, Hyperinsulinemia-how innocent a bystander? Diabetes Care 16:56–70, 1993
Weintraub MS, Eisenberg S, Dietary fat clearance in normal subjects is regulated by genetic variation in apolipoptotein E. J Clin Invest 86:1306–1311, 1987
Cohn JS, Johnson EJ, Millar JS, Cohn SD, Milne RW, Marcel YL et al, Contribution of apo B-48 and apo B-100 triglyceriderich lipoproteins (TRL) to postprandial increases in the plasma concentration of TRL triglycerides and retinyl esters. J Lipid Res 34:2033–2040, 1993
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Curtin, A., Deegan, P., Owens, D. et al. Elevated triglyceride-rich lipoproteins in diabetes. Acta Diabetol 33, 205–210 (1996). https://doi.org/10.1007/BF02048544
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02048544