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Biomedical subjects

M R Taskinen

Publications and source records attributed to M R Taskinen.

At least 55 records · Page 3Linked to original sources
PubMed1991

Demonstration of a novel feedback mechanism between FFA oxidation from intracellular and intravascular sources.

We examined the regulation of intracellular and intravascular lipolysis in vivo. In the first series of studies, plasma free fatty acids (FFA) were elevated moderately by heparin (plus approximately 600 mumol/l) in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in normal subjects. The increase in plasma FFA increased plasma FFA oxidation "submaximally" (plasma FFA oxidation less than 100% of total lipid oxidation) in a plasma FFA concentration-dependent manner. The increase in plasma FFA oxidation significantly suppressed direct intracellular oxidation of FFA. In another group of patients with NIDDM, plasma FFA was markedly increased (plus approximately 1,500 mumol/l). Plasma FFA oxidation now accounted for all lipid oxidation. Compared with substrate oxidation rates observed at submaximally elevated plasma FFAs in the same subjects at similar insulin concentrations, total lipid oxidation increased, carbohydrate oxidation decreased, and total energy production increased. These data demonstrate the existence of an FFA-dependent insulin-independent feedback mechanism between FFA oxidation from intracellular and intravascular sources. Thus the preferred response of body tissues to a change in plasma FFA oxidation is a reciprocal change in direct intracellular FFA oxidation. Substrate competition between carbohydrate and lipid, as proposed by P. J. Randle et al. (Lancet 1:785, 1963), becomes operative after the capacity for regulation within components of lipid oxidation has been utilized.

Blood Glucose↗
PubMed1990

Hyperlipidaemia in diabetes.

Currently our knowledge of the role of lipid abnormalities as risk factors for CHD in diabetes is insufficient. We need to define exact risk parameters to target correctly the therapy of lipid disorders and to outline optimum therapeutic strategies. Therefore it is necessary to identify quantitative and qualitative abnormalities of lipoproteins and apoproteins which signify the risk of CHD and to define their predictive power in prospective trials. Obviously we need to know more about the pathophysiology of lipid abnormalities and the action of insulin. Because diabetic patients carry a high inherent risk of CHD, target values recommended for non-diabetic populations may not be optimal for diabetic populations, but should be lower. To date no primary or secondary intervention trials in diabetic populations have been carried out to show that the lowering of lipid values (serum and LDL cholesterol) will reduce the risk of CHD morbidity or mortality or will prevent the progression of CHD in diabetes. Since hypertriglyceridaemia and low HDL levels are typical abnormalities in NIDDM it is a unique target group to test whether lowering of triglycerides and raising of HDL cholesterol levels will reduce the risk of CHD. Therefore there is a pressing need for clinical trials in both IDDM and NIDDM to provide adequate information on the benefits of lipid-lowering therapy and to confirm treatment strategies.

Apolipoproteins↗
PubMed1990

Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM.

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.

Aged↗
PubMed1989

Short-term effects of moderate alcohol consumption on lipid metabolism and energy balance in normal men.

The short-term effects of moderate alcohol consumption on energy balance, serum lipids, and lipoproteins were studied in eight healthy middle-aged men (age 30 to 47 years and body mass index 23.1 to 27.7 w/h2). A crossover dietary trial included two isocaloric periods without (20% protein, 50% carbohydrate, 30% fat) or with alcohol (12% protein, 29% carbohydrate, 25% fat, 75 g of alcohol as red wine). Each period lasted 2 weeks. The body weight of the subjects remained stable over the study. Fasting blood glucose, serum insulin, total cholesterol, and LDL cholesterol were similar at the end of both dietary periods. Mean values of serum total triglyceride (108 +/- 18 v 85 +/- 24 mg/dL, P less than 0.05), VLDL-Tg (88 +/- 24 v 73 +/- 16 mg/dL, NS), and total HDL cholesterol (49.4 +/- 6.0 v 43.4 +/- 5.5 mg/dL, P less than 0.05) were higher after the diet with alcohol than without alcohol. The increase of HDL cholesterol was primarily due to that of HDL2 cholesterol (10.4 +/- 5.1 v 5.7 +/- 3.9 mg/dL, P less than 0.05). The concentration of apoprotein A-I, A-II, and B averaged 104 +/- 17 v 89 +/- 16 mg/dL, 33 +/- 4 v 28 +/- 8 mg/dL, P less than 0.02, and 111 +/- 24 v 105 +/- 33 mg/dL after the diets with and without alcohol, respectively. Adipose tissue LPL activity increased in six of the eight volunteers during the diet with alcohol. Resting metabolic rate, postprandial energy expenditure, and postprandial responses of blood glucose, serum insulin, triglyceride, and plasma FFA were similar after the both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Insulin inhibition of overnight glucose production and gluconeogenesis from lactate in NIDDM.

Increased gluconeogenesis contributes to fasting hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM). We examined whether insulin inhibits gluconeogenesis from lactate by altering the fate of lactate and/or by reducing lactate flux. Seven patients with NIDDM (age 51 +/- 4 yr, body mass index 28 +/- 2 kg/m2) were studied before and 3 wk after achieving normoglycemia with evening insulin therapy. Basal glucose production (Ra) and utilization were measured overnight [( 3-3H]glucose infusion from 9 P.M. to 8 A.M.) and lactate turnover and conversion to glucose between 4 and 8 A.M. [( U-14C]lactate infusion) before and after insulin therapy. During insulin therapy, fasting plasma glucose decreased from 188 +/- 13 to 99 +/- 7 mg/dl (P less than 0.001) due to inhibition of glucose Ra from 3.0 +/- 0.1 to 2.2 +/- 0.1 mumol.kg-1.min-1 (P less than 0.005). Plasma free insulin increased from 6 +/- 1 to 11 +/- 1 microU/ml (P less than 0.005). Plasma lactate concentrations (1.1 +/- 0.2 vs. 1.0 +/- 0.1 mmol/l before vs. after insulin therapy) and the lactate turnover rate (15.6 +/- 0.9 vs. 14.2 +/- 0.8 mumol.kg.min) remained unchanged, whereas the amount of glucose formed from lactate decreased from 2.0 +/- 0.1 to 1.4 +/- 0.2 mumol.kg-1.min-1 (P less than 0.02) and the percent of lactate turnover converted to glucose decreased from 26 +/- 1 to 20 +/- 2% (P less than 0.05). We conclude that insulin inhibits overnight glucose Ra from lactate by decreasing the proportion of lactate diverted towards gluconeogenesis rather than by altering lactate availability or total flux.

Adult↗
PubMed1989

Bedtime insulin for suppression of overnight free-fatty acid, blood glucose, and glucose production in NIDDM.

We studied the clinical effectiveness and mechanism underlying the glucose-lowering effect of evening insulin therapy. Nocturnal profiles of blood glucose, plasma free fatty acid (FFA), glycerol, and lactate and overnight glucose kinetics [( 3-3H] glucose infusion) were measured in 15 non-insulin-dependent diabetic (NIDDM) patients with a relative body weight of 128 +/-4% who were poorly controlled with oral therapy alone. The patients were studied before and 2 wk and 3 mo after bedtime insulin (23 +/- 3 IU) was given in addition to oral therapy. An early-morning rise in blood glucose (greater than 31 mg/dl = 1.5 mM) was present in two-thirds of the patients and was associated with an overnight rise in plasma FFA and an increase in glucose production (Ra) during the early-morning hours (change 0.42 +/- 0.10 mg.kg-1.min-1, P less than .05, between 0300 and 0800). The overnight mean levels of blood glucose, plasma FFA, and serum insulin averaged 212 +/- 9 vs. 137 +/- 11 vs. 133 +/- 11 mg/dl (P less than .001), 674 +/- 61 vs. 491 +/- 57 vs. 484 +/- 36 microM (P less than 0.01) and 12.7 +/- 1.6 vs. 18.1 +/- 2.2 vs. 20.7 +/- 2.4 microU/L (P less than .01) before and 2 wk and 3 mo after the combination therapy. The decrements in overnight glucose and FFA levels after 2 wk of bedtime insulin therapy were closely correlated (r = .86, (P less than .001). The nocturnal profile of plasma lactate was similar before and during bedtime insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia.

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.

Adult↗
PubMed1988

Effect of insulin treatment on fatty acids of plasma and erythrocyte membrane lipids in type 2 diabetes.

Serum lipoproteins and fatty acid compositions of serum and erythrocyte membrane lipids were analyzed from sixteen Type 2 diabetic subjects with secondary drug failure before and after four weeks' insulin therapy. The insulin treatment clearly improved diabetic control (p less than 0.01), decreased serum total cholesterol (-14%, p less than 0.01), triglycerides (-50%, p less than 0.001), plasma free fatty acids (-28%, p less than 0.01), and especially serum VLDL-triglyceride levels (-62%, p less than 0.001) and resulted in a significant weight gain of patients (1.4 kg, p less than 0.05). Of the individual plasma fatty acids saturated (-32%) and monoenoic (-36%) fatty acids fell more than the polyunsaturated fatty acids of exogenous origin, eg linoleic acid (-11%), other n-6 polyunsaturated fatty acids (PUFA) (-11%), and n-3 PUFA (-13%) suggesting that the decrease in serum VLDL-triglycerides is mainly associated with the suppression of endogenous fatty acids. Before the insulin treatment but less strongly during it, the contents of linoleic acid were positively and those of dihomogammalinolenic acid, arachidonic acid, and arachidonic acid/linoleic acid ratios of plasma and erythrocyte membrane lipids inversely correlated with glycosylated HbA1 levels, suggesting that the conversion of linoleic acid to prostanoid precursor fatty acids is affected by the poor glycemic control in Type 2 diabetic patients.

Adult↗
PubMed1988

Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males.

We studied the effects of testosterone substitution on serum concentrations of lipids, lipoproteins, apoproteins and on the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma and on the activity of LPL in adipose tissue (AT-LPL) in 13 male hypopituitary patients. The activities of LPL and HL in postheparin plasma were markedly increased by 1 week after a testosterone enanthate injection (P less than 0.001). The HL activity remained elevated (P less than 0.05) after 1 month's treatment, but the LPL activity declined to presubstitution levels. The prolonged substitution decreased serum apoproteins A-I and A-II (P less than 0.05). The changes of apo A-I and A-II correlated inversely with those of the free testosterone index (FTI) (r = -0.74, r = -0.67, P less than 0.05). Serum HDL-cholesterol level decreased slightly by 1 week and it correlated inversely with the increase in testosterone and the FTI (r = -0.67, r = -0.85, P less than 0.05). The results suggest that testosterone increases the activity of both lipolytic enzymes in postheparin plasma. The effect on HL appears to be more persistent than that on LPL. The data support a role for androgens in the regulation of serum lipoprotein and HDL-cholesterol levels.

Adipose Tissue↗
PubMed1988

Effects of acipimox on serum lipids, lipoproteins and lipolytic enzymes in hypertriglyceridemia.

Two separate studies were carried out with acipimox, a new antilipolytic agent with long-lasting activity. First, in a randomized, double-blind, cross-over study a dose of 750 mg/day of acipimox versus placebo was employed for 60 days in 11 patients with type IV hyperlipoproteinemia. Mean plasma triglyceride levels were reduced after acipimox compared to placebo (434 +/- 60 vs 777 +/- 224 mg/dl, P less than 0.01). Serum total cholesterol fell also significantly after acipimox compared to placebo. No significant alteration was observed in the HDL2/HDL3 ratio or in the concentration or composition of the HDL subfractions. Six patients with severe hypertriglyceridemia (2 type IV and 4 type V) and low lipoprotein lipase (LPL) activity took part in a second, open study, lasting for 9 months. Acipimox was given at a dose of 750 mg/day for the first 6 months and 1200 mg/day for the last period. The response of serum total and VLDL triglycerides was inconsistent. HDL cholesterol was significantly raised (+33.3%) after 9 months of treatment due to changes of HDL2 and HDL3 cholesterol, phospholipid and protein concentrations. LPL activity was markedly reduced in adipose tissue at 9 months. No significant changes occurred in postheparin plasma LPL activity. In contrast, hepatic lipase activity showed a reduction of about 25% from 6 months of treatment onwards.

Adult↗
PubMed1988

XbaI and c/g polymorphisms of the apolipoprotein B gene locus are associated with serum cholesterol and LDL-cholesterol levels in Finland.

Several restriction fragment length polymorphisms (RFLPs) have been identified within or adjacent to the gene locus for apolipoprotein B (apo B), the major protein component of serum low density lipoprotein (LDL). One of these, detected with the restriction enzyme XbaI, has been suggested to be involved in the determination of serum lipid levels in some but not all populations. We determined the XbaI genotypes and serum lipoprotein levels of 176 apparently healthy unrelated Finns. Subjects homozygous (genotype X2X2) or heterozygous (genotype X1X2) for the presence of the XbaI restriction site within the apolipoprotein B gene (n = 113) had, on the average, an 11% higher serum total cholesterol (P = 0.01) level than those homozygous for the absence of this site (genotype X1X1, n = 63). In addition, the X2 allele was significantly associated with apo B(c), another allele reportedly associated with elevated serum cholesterol levels. The combined genotype (both X2 and apo B(c) alleles present) resulted in a greater elevation of total cholesterol (P = 0.004, when compared to subjects with neither allele) and LDL-cholesterol (P = 0.02) than the presence of either allele alone. The results suggest that both the XbaI and apo B(c/g) sites are in linkage disequilibrium with a functionally important DNA alteration within or adjacent to the apo B gene but the XbaI locus may be in stronger linkage disequilibrium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Elevated adipose tissue lipoprotein lipase activity in craniopharyngioma patients.

The activity of lipoprotein lipase (LPL) was measured in adipose tissue (AT-LPL) and postheparin plasma (PH-LPL) of 13 obese patients (aged 11 to 31 years) who had surgery for craniopharyngioma 1 to 13 years earlier. AT-LPL activity (mean +/- SEM) was higher in them than in subjects matched with respect to age, sex, and relative body weight (4.6 +/- 1.1 v 2.1 +/- 0.4 mumol free fatty acids (FFA).h-1.g-1, P less than .05). The activity was also higher when expressed per fat cell.

Adipose Tissue↗
PubMed1988

Changes in serum lipoprotein pattern induced by acute infections.

To study the effects of acute infections on serum lipids and lipoproteins we measured the concentration and composition of different lipoproteins, apoproteins A-I, A-II, and B, and the activities of plasma postheparin lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) during acute and convalescence phase and after complete recovery in 72 infectious patients (33 with viral infection and 39 with bacterial infection). The mass concentrations of both low density lipoprotein (LDL) (P less than .001) and high density lipoprotein (HDL)2 (P less than .002) were reduced during acute infections due to the lowering of their cholesterol, phospholipid, and protein contents. The reduction of LDL cholesterol was maximal at the acute stage of infection (change -15%, P less than .001) while the reduction of HDL2 cholesterol was maximal during the convalescence (change -35%, P less than .001). During acute infections LDL became triglyceride-enriched (11.8 v 8.6%, P less than .0001) but cholesterol-poor (36.6 v 39.3%, P less than .0001). The ratio of HDL cholesterol/LDL cholesterol was significantly reduced during the convalescence (0.42 +/- 0.15 v 0.53 +/- 0.19, P less than .0001). The concentrations of apo A-I and apo A-II were decreased during acute infections (changes -22%, P less than .001, and -16%, P less than .001, respectively). The very low density lipoprotein (VLDL) was 18% higher during the convalescence period than after the recovery due to the elevations of VLDL triglycerides, cholesterol, and phospholipids. The activity of LPL was reduced both in the acute and convalescence phase, whereas that of HL was reduced only in the acute phase of infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Comparison of the effects of two different doses of alcohol on serum lipoproteins, HDL-subfractions and apolipoproteins A-I and A-II: a controlled study.

Our earlier studies have shown that heavy alcohol intake increases the serum concentration of HDL2. The present study aimed to test which HDL subfraction is affected by moderate alcohol intake, and to examine the time- and dose-dependency of alcohol-induced changes in serum lipoproteins. Therefore, 30 or 60 g day-1 of alcohol were given to 10 healthy male volunteers during two 3-week periods separated by an abstinence period of 3 weeks. Lipoproteins were fractioned by sequential flotation. On both doses the total HDL3 concentrations rose progressively, the maximum increases being 10 and 25% at the end of respective drinking periods. In contrast, the HDL2 increased slightly only on the dose of 60 g day-1. The serum concentrations of apoprotein A-I and A-II increased on both doses but significantly only on the dose of 60 g day-1; the increments being 22 and 35%, respectively. On the basis of these and our earlier findings we conclude that (i) the effects of heavy and moderate alcohol intake on serum HDL-subfractions are different: the former preferentially increases the HDL2 whereas the latter augments the HDL3; (ii) alcohol-induced changes in serum lipoproteins are both time- and dose-dependent.

Adult↗
PubMed1988

Acute effects of ethanol and acetate on glucose kinetics in normal subjects.

We compared the effects of two ethanol doses on glucose kinetics and assessed the role of acetate as a mediator of ethanol-induced insulin resistance. Ten normal males were studied on four occasions, during which either a low (blood ethanol 4 +/- 1 mmol/l) or moderate (14 +/- 1 mmol/l) ethanol, acetate, or saline dose was administered. Both ethanol doses similarly inhibited (0.4-0.5 mg.kg-1.min-1, P less than 0.01) basal glucose production. The decrease in Ra was matched by a comparable decrease in glucose utilization (Rd), resulting in maintenance of normoglycemia. During hyperinsulinemia (approximately 70 microU/ml), glucose disposal was lower (1.2-1.7 mg.kg-1.min-1, P less than 0.01) in the moderate than the low-dose ethanol or saline studies. During acetate infusion, the blood acetate level was comparable with those in the ethanol studies. Acetate had no effect on glucose kinetics. In conclusion, 1) in overnight fasted subjects, ethanol does not cause hypoglycemia because its inhibitory effect on Ra is counterbalanced by equal inhibition of Rd;2) basal Ra and Rd are maximally inhibited already by small ethanol doses, whereas inhibition of insulin-stimulated glucose disposal requires a moderate ethanol dose; and 3) acetate is not the mediator of ethanol-induced insulin resistance.

Acetates↗
PubMed1988

Lipoproteins, lipolytic enzymes, and hormonal status in hypothyroid women at different levels of substitution.

Serum lipoproteins and postheparin plasma lipoprotein lipase and hepatic lipase (HL) activities were determined in 23 hypothyroid women treated with graded doses of thyroxine (T4) (50, 100, and 150 micrograms/day), each given for 3 weeks. Since the sex hormone-binding globulin (SHBG) and thereby serum sex steroid concentrations are sensitive to thyroid status, we also measured serum testosterone, estradiol, and SHBG at each time. Stepwise T4 treatment resulted in gradual improvement in thyroid status. Concomitantly, serum low density lipoprotein (LDL) cholesterol decreased in a linear fashion from a mean of 4.72 +/- 0.31 (+/- SEM) to 3.21 +/- 0.18 mmol/L (P less than 0.001) after the largest dose. In contrast, serum high density lipoprotein (HDL) cholesterol decreased, although not in a dose-dependent fashion, from 1.61 +/- 0.07 to 1.44 +/- 0.05 mmol/L (P less than 0.001) after the largest dose. Serum SHBG increased along with improvement of thyroid function, but this increase did not have major impact on the changes in LDL during T4 treatment, as judged by multiple regression analysis. Thus, serum LDL correlated independently only with T4 (r = -0.38; P less than 0.001). The serum HDL changes were almost exclusively due to those in the HDL2 subfraction, and these were related to HL activity, which increased from 13.4 +/- 1.76 to 18.9 +/- 2.08 U/L after the largest dose. We conclude that thyroid hormones regulated serum HDL (HDL2) cholesterol mainly through their effect on HL.

Adult↗