Summary
We have previously shown that lipoprotein lipase (LPL) activity of tissues is an important determinant not only of plasma VLDL levels but also of HDL-cholesterol. Studies were designed to investigate whether the serum lipoprotein alterations in uncontrolled insulin-deficient diabetes can be accounted for by changes in LPL activity of tissues. The heparin-releasable LPL activity was determined from biopsy samples of adipose tissue and skeletal muscle in 16 patients with newly detected untreated insulin-deficient diabetes and in 16 age-, sex- and body weight-matched healthy control subjects. Repeat assays were carried out after the patients had been on insulin treatment for an average of two weeks and when the diabetes was well controlled. When untreated the patients had increased concentrations of triglycerides and cholesterol in whole serum and in VLDL and LDL while the HDL cholesterol level was lower than that of controls (p<0.01). The cholesterol/triglyceride ratio in each of the three lipoproteins was similar in patients and controls. While untreated the diabetic patients had significantly reduced mean LPL activity both in adipose tissue (average 34% of control mean, p<0.001) and in skeletal muscle (average 45% of control mean, p<0.05). In the whole group HDL-cholesterol was positively correlated with adipose tissue LPL activity (r=+0.58, p<0.001) while log serum total triglyceride and log VLDL-triglyceride showed significant negative correlations with LPL activity of both adipose tissue and skeletal muscle. After initiation of insulin treatment the LPL activity increased significantly (p<0.01) in both tissues but was still subnormal after 2 weeks. At the same time the VLDL and LDL concentrations had returned to normal while the HDL-cholesterol remained low. The results suggest that the increase of VLDL and LDL triglyceride and the decrease of HDL-cholesterol present in uncontrolled insulin-deficient diabetes are, at least partly, accounted for by decreased LPL activity of tissues. The restoration of tissue LPL and of serum HDL-cholesterol by insulin are relatively slow processes. The results are consistent with the hypothesis that HDL-cholesterol concentration is dependent on the efficiency of removal of triglyceride-rich lipoproteins from the circulation.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Nikkilä, E. A.: Triglyceride metabolism in diabetes mellitus. Progr. Biochem. Pharmacol.8, 271–299 (1973)
Tuller, E. F., Mann, G. V., Schertenleib, F., Roehrig, C. B., Root, H. F.: The effect of diabetic acidosis and coma upon the serum lipoproteins and cholesterol. Diabetes3, 279–286 (1954)
Kolb, F. O., de Lalla, O. F., Gofman, J. W.: Thehyperlipemias in disorders of carbohydrate metabolism: serial lipoprotein studies in diabetic acidosis with xanthomatosis and in glycogen storage disease. Metabolism4, 310–317 (1955)
Lewis, B., Mancini, M., Mattock, M., Chait, A., Fraser, T. R.: Plasma triglyceride and fatty acid metabolism in diabetes mellitus. Eur. J. Clin. Invest.2, 445–453 (1972)
Nikkilä, E. A., Kekki, M.: Plasma triglyceride transport kinetics in diabetes mellitus. Metabolism22, 1–22 (1973)
Nikkilä, E. A., Huttunen, J. K., Ehnholm, C.: Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism. Diabetes26, 11–21 (1977)
Documenta Geigy Scientific Tables: Mean and ideal body weights of adults. 6th ed., p. 588. Basle: J. R. Geigy S. A. 1960
Belfrage, P., Vaughan, M.: Simple liquid-liquid partition system for isolation of labeled oleic acid from mixtures with glycerides. J. Lipid Res.10, 341–344 (1969)
Taskinen, M.-R., Nikkilä, E. A.: Lipoprotein lipase activity in adipose tissue and in postheparin plasma in human obesity. Acta Med. Scand.202, 399–408 (1977)
Hyvärinen, A., Nikkilä, E. A.: Specific determination of blood glucose with o-toluidine. Clin. Chim. Acta7, 140–143 (1962)
Herbert, V., Lau, K.-S., Gottlieb, C. W., Bleicher,. S. J.: Coated charcoal immunoassay of insulin. J. clin. Endocrinol. Metab.25, 1375–1384 (1965)
Enzymatic Colorimetric Method Cat. No. 187313: Test-Combination Cholesterol. Boehringer Mannheim GmbH, Diagnostica
Kessler, G., Lederer, H.: In: Automation in analytical chemistry. Skeggs, L. T. (Ed.), p. 342. Technicon Symposium 1966
Havel, R. J., Eder, H. A., Bragdon, J. H.: The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J. Clin. Invest.34, 1345 (1955)
Schonfeld, G., Birge, C., Miller, J. P., Kessler, G., Santiago, J.: Apolipoprotein B levels and altered lipoprotein composition in diabetes. Diabetes23, 827–834 (1974)
Lopes-Virella, M. F. L., Stone, P. G., Colwell, J. A.: Serum high density lipoprotein in diabetic patients. Diabetologia13, 285–291 (1977)
Paisey, R., Elkeles, R. S., Hambley, J., Magill, P.: The effects of chlorpropamide and insulin on serum lipids, lipoproteins and fractional triglyceride removal. Diabetologia15, 81–85 (1978)
Howard, B. V., Savage, P. J., Bennion, L. J., Bennett, P. H.: Lipoprotein composition in diabetes mellitus. Atherosclerosis30, 153–162 (1978)
Nikkilä, E. A., Hormila, P.: Serum lipids and lipoproteins in insulin treated adult diabetics. Demonstration of increased high density lipoprotein levels. Diabetes27, 1078–1086 (1978)
Calvert, G. D., Graham, J. J., Mannik, T., Wise, P. H., Yeates, R. A.: Effects of therapy on plasma-high-density-lipoprotein-cholesterol concentration in diabetes mellitus. Lancet1978 II, 66–68
Pykälistö, O. J., Smith, P. H., Brunzell, J. D.: Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity. J. Clin. Invest.56, 1108–1117 (1975)
Persson, B., Hood, B., Angervall, G.: Effects of prolonged fast on lipoprotein lipase eluted from human adipose tissue. Acta Med. Scand.188, 225–230 (1970)
Taskinen, M.-R., Nikkilä, E. A.: Effects of caloric restriction on lipid metabolism in man: Changes of tissue lipoprotein lipase activities and of serum lipoproteins. Atherosclerosis32, 289–299 (1979)
Nilsson-Ehle, P., Carlström, S., Belfrage, P.: Rapid effects on lipoprotein lipase activity in adipose tissue of humans after carbohydrate and lipid intake. Time course and relation to plasma glycerol, triglyceride, and insulin levels. Scand. J. Clin. Lab. Invest.35, 373–378 (1975)
Nikkilä, E. A., Taskinen, M.-R.: Unpublished observations
Weisenburg Delorme, C. L., Harris, K. L.: Effects of diet on lipoprotein lipase activity in the rat. J. Nutr.105, 447–451 (1975)
Linder, C., Chernick, S. S., Fleck, T. R., Scow, R. O.: Lipoprotein lipase and uptake of chylomicron triglyceride be skeletal muscle of rats. Am. J. Physiol.231, 860–864 (1976)
Tan, M. H., Sata, T., Havel, R. J.: The significance of lipoprotein lipase in rat skeletal muscles. J. Lipid Res.18, 363–370 (1977)
Cryer, A., Riley, S. E., Williams, E. R., Robinson, D. S.: Effect of nutritional status on rat adipose tissue, muscle and postheparin plasma clearing factor lipase activities: their relationship to triglyceride fatty acid uptake by fat-cells and to plasma insulin concentrations. Clin. Sci. Mol. Med.50, 213–221 (1976)
Nikkilä, E. A., Taskinen, M.-R., Kekki, M.: Relation of plasma high-density lipoprotein cholesterol to lipoprotein-lipase activity in adipose tissue and skeletal muscle of man. Atherosclerosis29, 497–501 (1978)
Nikkilä, E. A.: Metabolic and endocrine control of plasma high density lipoprotein concentration. Relation to catabolism of triglyceride-rich lipoproteins. In: High density lipoproteins and atherosclerosis. Gotto, Jr., A. M., Miller, N. E., Oliver, M. F. (Eds.), p. 177. Amsterdam: Elsevier/North-Holland Biomedical Press 1978
Taskinen, M.-R., Hynd, B. A., Robertson, K., Glueck, C. J.: Postheparin plasma lipoprotein lipase in familial hyperalphalipoproteinemia: Relationship with HDL cholesterol. Circulation (abstract) (in press)
Nikkilä, E. A.: The effect of heparin on serum lipoproteins. Scand. J. Clin. Lab. Invest.4, 369–370 (1952)
Patsch, J. R., Gotto, A. M. Jr., Olivecrona, T., Eisenberg, S.: Formation of high density lipoprotein-2-like particles during lipolysis of very low density lipoproteins invitro. Proc. Natl. Acad. Sci. USA75, 4519–4523 (1978)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Taskinen, M.R., Nikkilä, E.A. Lipoprotein lipase activity of adipose tissue and skeletal muscle in insulin-deficient human diabetes. Diabetologia 17, 351–356 (1979). https://doi.org/10.1007/BF01236268
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01236268