M Kekki

University of Helsinki, Helsinki, Southern Finland Province, Finland

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Publications (38)146.13 Total impact

  • M Kekki
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    ABSTRACT: In a series of healthy normolipaemic, adult subjects, plasma triglyceride turnover, heparin-releasable lipoprotein lipase (LPL), and plasma HDL cholesterol were determined. Strong correlations were found to exist between the fractional removal rate of plasma triglycerides (FTR) or LPL as one variable and HDL cholesterol as the other, whereas the triglyceride turnover rate (TR) did not correlate with HDL cholesterol. It is concluded that lipoprotein lipase action is largely responsible for the formation of HDL cholesterol in the blood stream.
    Atherosclerosis 10/1980; 37(1):143-50. · 3.71 Impact Factor
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    ABSTRACT: Lipoprotein-lipase activity (LPL) was measured in biopsies of adipose tissue and skeletal muscle of normal human subjects, and the results were related to concentrations of cholesterol and triglycerides in plasma lipoproteins. Adipose-tissue LPL activity was significantly higher in females than in males, whereas no sex difference was observed in skeletal-muscle LPL activity. A highly significant positive correlation was present between the plasma high density lipoprotein (HDL) cholesterol level and LPL activity in adipose tissue (r = +0.66, P less than 0.001) but not between HDL and skeletal-muscle LPL. The results suggest that the activity of LPL in adipose tissue and the rate of catabolism of triglyceride-rich lipoproteins might be one of the factors that determine the concentration of HDL in plasma and at least partly account for the known sex difference in plasma HDL level.
    Atherosclerosis 05/1978; 29(4):497-501. · 3.71 Impact Factor
  • Advances in experimental medicine and biology 02/1977; 82:146-8. · 1.83 Impact Factor
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    ABSTRACT: 1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism. 2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase. 3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides. 4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides. 5. The mean activity of post-heparin plasma lipo-protein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases. 6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal.
    Clinical science and molecular medicine 05/1976; 50(4):249-60.
  • M Kekki, U Attila, S Talanti
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    ABSTRACT: Thirst stimulation of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) was induced in rats by withholding all fluids during three days. 35S-cysteine was then intraperitoneally administered and the rats were killed at predetermined times and examined by autoradiography, applying the authors' previously described method. This experimental series totalling 51 animals was compared with a control series of 70 rats, similarly treated, who had had free access to water. The kinetic phenomena in SON and PVN were analysed in terms of the two-compartment model previously used, which gives an estimate of the neurosecretory material (NSM) secretion parameters and of those of the lumped structural cell protein turnover in the nuclei. The kinetics of the precursor amino acids after administration of labelled cysteine were also assessed. Determinations of the label uptake at two specific times in the experiment, in the infundibular nucleus, ventromedial nucleus and optic nerve tissue in both series served as a check on the specifity of the structural protein turnover changes observed. Compared with the controls, the turnover rate of the slow compartment was more than tripled in the dehydrated rats, while that of the fast compartment had gone down to about one-third; both effects very nearly equal in SON and PVN. These results are compatible with the concept according to which thirst stimulates the SON and PVN equally. A distinct, and strikingly equal, hump was observed (2 hours after label administration) in all specific activity curves, also in the precursor serum concentration, and it is probably due to recycling of 35s from cysteine to methionine. This and other circumstances render the phenomena rather too complex for a straight-forward evaluation by the two-compartment model. Even so, the observations are believed to furnish good evidence of the biological verity of this model as well as the thirst-induced changes elicited.
    Cell and Tissue Research 06/1975; 158(4):439-50. · 3.68 Impact Factor
  • M Kekki, E A Nikkilä
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    ABSTRACT: Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg - kg-1- hr-1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg - kg-1 - hr-1. A highly significant correlation was present between the two turnover rates (r equal + 0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics.
    Scandinavian Journal of Clinical and Laboratory Investigation 04/1975; 35(2):171-9. · 1.29 Impact Factor
  • M. Kekki, E. A. Nikkilä
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    ABSTRACT: Kekki, M. & Nikkilä, E. A. Turnover of Plasma Total and Very Low Density Lipoprotein Triglyceride in Man. Scand. J. clin. Lob. Invest. 35, 171–179, 1975. Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg. kg−l. hr−1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg · kg−1. hr−1. A highly significant correlation was present between the two turnover rates (r = +0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics.
    Scandinavian Journal of Clinical & Laboratory Investigation - SCAND J CLIN LAB INVEST. 01/1975; 35(2):171-179.
  • M. Kekki, U. Attila, S. Talanti
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    ABSTRACT: Thirst stimulation of the supraoptic nucleus (SON) and paraventricular nucleus (PVN) was induced in rats by withholding all fluids during three days. 35S-cysteine was then intraperitoneally administered and the rats were killed at predetermined times and examined by autoradiography, applying the authors' previously described method. This experimental series totalling 51 animals was compared with a control series of 70 rats, similarly treated, who had had free access to water. The kinetic phenomena in SON and PVN were analysed in terms of the two-compartment model previously used, which gives an estimate of the neurosecretory material (NSM) secretion parameters and of those of the lumped structural cell protein turnover in the nuclei. The kinetics of the precursor amino acids after administration of labelled cysteine were also assessed. Determinations of the label uptake at two specific times in the experiment, in the infundibular nucleus, ventromedial nucleus and optic nerve tissue in both series served as a check on the specifity of the structural protein turnover changes observed.
    Cell and Tissue Research - CELL TISSUE RES. 01/1975; 158(4):439-450.
  • E A Nikkilä, M Kekki
    Metabolism 02/1973; 22(1):1-22. · 3.10 Impact Factor
  • Esko A. Nikkilä, Matti Kekki
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    ABSTRACT: Plasma endogenous triglyceride transport has been measured in 74 adult patients with different types of diabetes and compared to similar data obtained in 35 healthy normoglyceridemic control subjects. The diabetic material was divided into subgroups by a number of criteria including ketoacidosis, insulin-dependence, relative body weight, control of blood glucose, and severity of hypertriglyceridemia. In ketoacidosis, a marked elevation of plasma triglyceride production rate was the rule, and this probably accounted for the moderate hypertriglyceridemia even though the fractional transport was simultaneously lowered. In uncontrolled but nonketotic juvenile-type diabetes the mean plasma triglyceride turnover rate and concentration were both significantly increased while the fractional turnover was in most cases within normal range. When the disease was brought into good control by insulin the production rate decreased but not completely in line with blood glucose. Patients with adult-onset-type diabetes showed also an increase of triglyceride turnover rate, and the magnitude of hypertriglyceridemia was consistent with this increment so that most patients were “on line” of the enzyme kinetic Michaelis curves extrapolated from the normal material. On the other hand, of nonketotic diabetics with severe hyperglyceridemia (more than 4.0 mM) some had an increased turnover rate, while others were characterized by a normal production rate. Therefore, it is probable that one minor group of diabetics has a true removal defect, while in other forms of diabetes, the hypertriglyceridemia, if present, is primarily due to enhanced hepatic secretion of triglycerides into plasma. The exogenous fat tolerance was tested in 15 uncontrolled diabetics and 10 control subjects with intravenous intralipid emulsion. The fractional disappearance rate was either normal or decreased in diabetes but, when compared at similar basal plasma triglyceride concentration, there was no difference in the elimination of exogenous particulate fat between diabetics and nondiabetics. The different mechanisms of hypertriglyceridemia associated with diabetes are discussed on the basis of the results obtained in this study. In this connection a new concept on the regulation of removal kinetics by plasma triglyceride production rate is suggested.
    Metabolism. 01/1973;
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    E A Nikkilä, M Kekki
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    ABSTRACT: Plasma endogenous triglyceride transport kinetics were determined in 16 hyperthyroid and in 12 hypothyroid patients and the results compared with those of euthyroid control subjects. In addition, the removal of exogenous particulate fat (Intralipid; Vitrum, Sweden) from the circulation and the postheparin plasma lipolytic activity (PHLA) were studied in these patients for further characterization of the alterations of plasma triglyceride metabolism in thyroid disease. In thyrotoxicosis the average plasma triglyceride level was slightly but significantly increased above that of control subjects. This change was associated with augmented production of triglycerides whereas the mean fractional removal rate was not different from normal. There was a significant linear correlation between the concentration and turnover rate of plasma triglycerides in both hyperthyroid and euthyroid subjects but the concentration/turnover rate ratio was less in the former group suggesting that the efficiency of removal of triglycerides from the circulation was improved in thyroid hyperfunction. The elimination of intravenously administered particulate fat occurred more rapidly in untreated hyperthyroid patients than in euthyroid control subjects. The mean PHLA was also above normal in thyrotoxicosis. Upon adequate treatment of the hyperthyroid state the fasting plasma triglyceride concentration was further increased. Hypothyroid patients showed another pattern of alteration of triglyceride kinetics. The synthesis of plasma triglycerides was normal but the fractional removal of both endogenous and exogenous triglycerides was markedly reduced and this change seems to account for the hypertriglyceridemia associated with thyroid hypofunction. The plasma PHLA was also clearly decreased in the hypothyroid state. Plasma FFA and glycerol levels were increased in hyperthyroidism and plasma FFA was slightly decreased in hypothyroid patients, but these variables were not significantly correlated with any parameter of triglyceride metabolism. Endogenous triglyceride turnover rate was significantly correlated with serum protein-bound iodine (PBI) and T3 uptake in thyrotoxicosis but not in hypothyroidism. Removal of exogenous fat was not related to postheparin plasma lipolytic activity but the fractional endogenous triglyceride transport showed a highly significant relationship to this lipase activity in a mixed group of hyper- and hypothyroid patients. The results suggest that thyroid hormones control both production and removal of plasma triglycerides. Different mechanisms for these interactions are considered.
    Journal of Clinical Investigation 09/1972; 51(8):2103-14. · 12.81 Impact Factor
  • E A Nikkilä, M Kekki
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    ABSTRACT: . The kinetics of plasma endogenous triglyceride transport were assessed in nine hyperglyceridaemic patients before and after treatment with an effective hypolipidaemic compound of the clofibrate group, phenolic ether Su-13437. The triglyceride turnover was measured by endogenous 3H-glycerol labelling technique and the results were compared to those obtained earlier in selected normal subjects. In the untreated stage the plasma triglyceride transport (production) rate was above the normal range in seven of the nine patients but it did not correlate with the triglyceride concentration. On the other hand, the logarithm of the concentration showed a significant inverse correlation with the fractional transport rate. During administration of the drug both the plasma triglyceride concentration and production rate fell in all subjects, the mean decreases being 52 and 35%, respectively. The response of the fractional transport rate to treatment was very variable and although the mean increase of 26% was significant the change did not correspond to the decrease in the triglyceride concentration. On the basis of these observations it is suggested that the primary defect in most cases of type IV endogenous hyperglyceridaemia is an increased inflow transport of plasma triglycerides but the actual plasma triglyceride level is ultimately determined by the inherent type of transport kinetics. The compound Su-13437 is an effective triglyceride-concentration-lowering agent which acts mainly by decreasing the production of plasma triglycerides.
    European Journal of Clinical Investigation 07/1972; 2(4):231-8. · 3.37 Impact Factor
  • S Talanti, U Attila, M Kekki
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    ABSTRACT: The fate of 35S-cysteine incorporated into the hypothalamic-hypophyseal neurosecretory system was followed in normal rats as a function of time from 30 min up to 30 hrs after intraperitoneal administration (11 different times, three rats each). Autoradiography and grain counting were employed to determine quantitatively the activities present in: supraoptic nucleus (SON), paraventricular nucleus (PVN), three different sites in the hypothalamic-hypophyseal tract (HHT), corresponding to its initial, middle and late portions, and neurohypophysis (NH). In SON and PVN, the kinetic behaviour of 35S-cysteine was compatible with a two-compartment model, implying decline of tracer activity in accordance with two exponential components. Of these, the slow throughput component had its closely equivalent, apparently independent, counterparts in the HHT and NH. Replicas of the rapidly abating activity peak were seen, superimposed on the slow component, in the HHT with such timing of its appearance at the various sites, as to be consistent with the concept of travel through the HHT, at substantially constant speed and without delay, of material rich in 35S-cysteine that has been primarily synthesized in the SON and PVN (with the “transport theory of neurosecretion”). This flow was calculated to have a velocity in the order of 0.6 mm per hour. The kinetic phenomena and their association with the supposed sites of synthesis, and transport, of the neurosecretory material are discussed with reference to earlier literature.
    Zeitschrift für Zellforschung und mikroskopische Anatomie (Vienna, Austria: 1948) 02/1972; 124(3):342-53.
  • E A Nikkilä, M Kekki
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    ABSTRACT: . Since fructose is now marketed as a nutrient a study has been initiated to compare the effects of fructose, sucrose and starch at a conventional dietary intake level on the plasma triglyceride concentration and turnover in patients with endogenous hypertriglyceridemia. Preliminary results are presented here.Fructose or sucrose in a daily amount of 75 to 80 grams were added to the diet in an isocaloric exchange for starch in twelve hyperglyceridemic patients under hospital conditions. Each dietary period lasted for 10 to 20 days and the triglyceride turnover was studied by endogenous glycerol labeling technique at the end of each period. Five of the patients had manifest diabetes managed by diet or oral antidiabetic drugs.Plasma triglyceride response to fructose was variable and the average change from the level observed during fructose-free diet was not significant. However, in nondiabetic subjects a definite rising trend of triglyceride was noticeable. Sucrose caused a significant increase of triglyceride concentration above that measured during fructose and starch diets. Diabetics were not included into the sucrose group, however. The fractional removal rate of plasma triglycerides was identical during all three diets but the triglyceride production rate showed a rising trend during fructose and, particularly, during sucrose diet as compared to starch. Because of the limited number of subjects studied so far, these results do not justify any definite conclusions.
    Acta medica Scandinavica. Supplementum 02/1972; 542:221-7.
  • M Kekki, E A Nikkilä
    Metabolism 10/1971; 20(9):878-89. · 3.10 Impact Factor
  • Matti Kekki, Esko A. Nikkilä
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    ABSTRACT: The effect of oral contraceptives on the concentration, production rate, and removal efficiency of plasma triglycerides was studied in premenopausal women using an endogenous labeling of triglycerides with tritiated glycerol. Thirteen subjects were studied while receiving the drug and seventeen normal healthy females served as controls. In some instances the study was made both before and during the drug or repeated after discontinuation of the treatment. The elimination of triglycerides from the circulation was characterized using the Michaelis constant, Km, which gives the plasma concentration at half-maximal removal velocity. The control group showed a polymorphism of plasma triglyceride kinetics being composed of three subgroups which had different maximal turnover rates. Treatment with oral contraceptives was associated with highly significant increases of concentration, rate of production, and efficiency of removal of plasma triglycerides whereas the maximal turnover rate was apparently unaffected. Thus, the increase of plasma triglyceride concentration (average 1.5-fold) observed in women receiving oral contraceptives is accounted for by a much enhanced influx (average 1.9-fold). The influence of the latter is partly compensated by a simulataneous acceleration of triglyceride efflux, however. The effects are produced already by one cycle of treatment but almost no reversion of the changes can be observed at 1 mo after discontinuation of the drug. The triglyceride concentration and production rate were significantly correlated to the duration of intake of contraceptive preparations while the removal efficiency was not.
    Metabolism. 09/1971;
  • M Kekki, E A Nikkilä
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    ABSTRACT: . The kinetic parameters of plasma triglyceride metabolism were determined in 14 adult subjects with the nephrotic syndrome by endogenous labelling of circulating triglyceride with tritiated glycerol. The triglyceride production (turnover) rate and the apparent Km of removal were calculated from the slope of the radioactivity disappearance curve and compared to a normal control material studied previously. Plotting of the individual data in a log scale of triglyceride concentration versus turnover with the normal area and saturation curves in the background allowed a detailed characterization of the nature of kinetic alterations occurring in disease. It was found that in the majority of cases with the nephrotic syndrome the plasma triglyceride concentration and rate of influx are slightly above normal. However, the apparent Km of removal was significantly increased suggesting that efflux may also be somewhat impaired. In four cases the plasma triglyceride was produced at a rate which exceeded the value predicted by the normal saturation curves and it is believed that an uncontrolled overproduction of plasma triglyceride was present in these cases.—Complete remission of disease in one case brought both triglyceride concentration and turnover rate rapidly to normal values. An eight-hour infusion of human serum albumin in another patient promptly caused a return of high triglyceride turnover to normal.— The primary change behind the nephrotic hypertriglyceridaemia seems to be a controlled increase of plasma triglyceride synthesis. In some cases, however, this overproduction occurs in an uncontrolled fashion and in a number of patients decrease of removal efficiency contributes to the development of hyperglyceridaemia. All of these changes can be explained on the basis of an increased FFA/albumin molar ratio in plasma giving rise to the elevation of unbound FFA fraction.
    European Journal of Clinical Investigation 06/1971; 1(5):345-51. · 3.37 Impact Factor
  • E A Nikkilä, M Kekki
    Scandinavian Journal of Clinical and Laboratory Investigation 05/1971; 27(2):97-104. · 1.29 Impact Factor
  • E A Nikkilä, M Kekki
    Annales medicinae experimentalis et biologiae Fenniae 02/1970; 48(4):246-8.
  • Annales chirurgiae et gynaecologiae Fenniae 02/1968; 57(1):1-8.