Lipoprotein Lipase Activity in Skeletal Muscle Is Related to Insulin ...

1202 Arteriosclerosis and Thrombosis Vol 11, No 5 September/October 1991
was expressed per gram. However, it may be questioned
that LPL activity should be expressed per 10 6
cells because we analyzed the heparin-releasable
(extracellular) part. Thus, by analogy, muscle LPL
activity should have been expressed per 10 6 muscle
fibers because muscle fiber size is also related to
obesity. However, we regard the significant correlations
between TG concentration in serum and muscle
LPL activity expressed per gram as an indication of
the importance of muscle LPL and as an indication
that this way of expressing the LPL activity is physiologically
relevant.
Hepatic lipase activity is known to be regulated by
sex steroids. For example, during treatment with estrogens,
activity of this enzyme is decreased, but when
estrogen is combined with a gestagen with androgenic
properties, hepatic lipase activity is upregulated, being
reflected primarily in increases and decreases, respectively,
in HDL cholesterol concentrations. 41 " 43 However,
an inverse relation between the degree of physical
fitness (Vo 2max ) and hepatic lipase activity has
been reported. 44 More physically fit men have lower
insulin concentrations than do less fit ones. 4546 These
observations are compatible with the present finding
of a positive correlation between the area under the
curve of insulin concentrations and hepatic lipase
activity. It is thus possible that insulin (or insulinrelated
cellular functions) may also be involved in the
regulation of hepatic lipase activity. It may be suggested
that the increases in hepatic lipase activity may
have been partly due to overexposure of the liver to
FFAs. This could induce hepatic insulin resistance,
further diminish hepatic insulin extraction, 3 - 31 - 32 and
reduce the hepatic catabolism of sex steroids. 47
In conclusion, this study has demonstrated that
muscle LPL activity is correlated with the serum TG
concentration in the fasting state and intravenous fat
tolerance, indicating a role for impaired hydrolysis of
circulating TGs in the hypertriglyceridemia of obesity
and diabetes. Furthermore, muscle LPL activity was
related to glucose infusion rate, suggesting that the
hyperinsulinemia associated with insulin resistance
may have a downregulating effect on muscle LPL
activity. The present results demonstrate that several
risk factors for coronary heart disease, such as serum
TG and HDL cholesterol concentrations and blood
pressure, are correlated with insulin resistance, supporting
the concept that insulin resistance is an
important underlying pathogenic condition.
References
1. Reaven GM: Role of insulin resistance in human disease.
Diabetes 1988;3:1595-1607
2. Modan M, Halkin H, Almog S, Lusky A, Eshkol A, Shefi M,
Shitrit A, Fuchs Z: Hyperinsulinemia: A link between hypertension,
obesity and glucose intolerance. / Clin Invest 1985;75:
809-817
3. Reaven GM, Grenfield S: Diabetic hypertriglyceridaemia:
Evidence for three clinical syndromes. Diabetes 1982;30(suppl
2):66-75
4. Taskinen MR, Beltz WF, Harper I, Fields RM, Schonfeld G,
Grundy SM, Howard BV: Effects of NIDDM on very-lowdensity
lipoprotein triglyceride and lipoprotein B metabolism:
Studies before and after sulfonylurea therapy. Diabetes 1986;
35:1268-1277
5. Robinson DS: The function of the plasma triglycerides in fatty
acid transport, in Florkin M, Stotz EH (eds): Comprehensive
Biochemistry. Amsterdam, Elsevier Science Publishing Co, Inc,
1970, vol 18, pp 51-116
6. Bolinder J, Lithell H, Skarfors E, Arner P: Effects of obesity,
hyperinsulinemia, and glucose intolerance on insulin action in
adipose tissue of sixty-year-old men. Diabetes 1986;35:282-290
7. Lithell H, Lindgarde F, Hellsing K, Lundqvist G, Nygaard E,
Vessby B, Saltin B: Body weight, skeletal muscle morphology,
and enzyme activities in relation to fasting serum insulin
concentration and glucose tolerance in 48-year-old men. Diabetes
1981;30:19-25
8. Lithell H, Krotkiewski M, Kiens B, Wroblewski Z, Holm G,
Strdmblad G, Grimby G, Bjorntorp P: Non-response of muscle
capillary density and lipoprotein-lipase activity to regular
training in diabetic patients. Diabetes Res 1985;2:17-21
9. Grimby G, Wilhelmsen L, Bjorntorp P, Saltin B, Tibblin G:
Habitual physical activity, aerobic power and blood lipids, in
Pernow B, Saltin B (eds): Muscle Metabolism During Exercise.
New York, Plenum Publishing Corp, 1971, pp 469-489
10. Pollare T, Lithell H, Selinus I, Berne C: Application of
prazosin is associated with an increase of insulin sensitivity in
obese patients with hypertension. Diabetologia 1988;31:
415-420
11. Ikkos D, Luft R: On the intravenous glucose tolerance test.
Ada Endocrinol (Copenh) 1957;25:312-334
12. Jeppsson J-O, Jerntorp P, Sundkvist G, Englund H, Nylund V:
Measurement of hemoglobin A]C by a new liquid-chromatography
assay: Methodology, clinical utility, and relation to
glucose tolerance evaluated. Clin Chem 1986;32:1867-1872
13. DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique:
A method for quantifying insulin secretion and resistance. Am
JPhysiol 1979;237:E214-E223
14. Altszuler N, Barkari A, Bjerknes C, Gottlieb B, Steele R:
Glucose turnover values in the dog obtained with various
species of labeled glucose. Am J Physiol 1975;229:1662-1667
15. Siegler L, Wu TW: Separation of serum high-density lipoprotein
for cholesterol determination: Ultracentrifugation vs precipitation
with sodium phosphotungstate and magnesium chloride.
Clin Chem 1981;27:838-841
16. Hirsch J, Goldrick RB: Serial studies on the metabolism of
human adipose tissue: I. Lipogenesis and free fatty acid
uptake and release in small aspirated samples of subcutaneous
fat. / Clin Invest 1964;43:1776-1792
17. Bergstrom J: Muscle electrolytes in man. Scand J Clin Lab
Invest 1962;14(suppl):l-110
18. Nilsson-Ehle P, Schotz MC: A stable radioactive substrate
emulsion for assay of lipoprotein lipase. / Lipid Res 1976;17:
536-541
19. Lithell H, Boberg J: A method of determining lipoproteinlipase
activity in human adipose tissue. Scand J Clin Lab Invest
1977;37:551-561
20. Lithell H, Boberg J: Determination of lipoprotein-lipase activity
in human skeletal muscle tissue. Biochim Biophys Ada
1978;528:58-68
21. Arner P, Engfeldt P, Lithell H: Site differences in the basal
metabolism of subcutaneous fat in obese women. / Clin
Endocrinol Metab 1981;53:948-952
22. Boberg J, Carlson LA: Determination of heparin-induced
lipoprotein lipase activity in human plasma. Clin Chim Ada
1964;10:420-427
23. Nilsson-Ehle P, Ekman R: Rapid, simple and specific assays
for lipoprotein lipase and hepatic lipase. Artery 1977;3:
194-209
24. Nilsson-Ehle P, Garfinkel AS, Schotz MC: Lipolytic enzymes
and plasma lipoprotein metabolism. Annu Rev Biochem 1980;
49:667-693
25. Carlson LA, Rossner S: A methodological study of an intravenous
fat tolerance test with Intralipid emulsion. Scand J Clin
Lab Invest 1972;29:271-280
Downloaded from http://atvb.ahajournals.org/ by guest on August 29, 2013