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Biomedical subjects

M R Taskinen

Publications and source records attributed to M R Taskinen.

At least 217 records · Page 12Linked to original sources
PubMed1985

Effect of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition in non-insulin-dependent diabetes mellitus.

To assess the effects of sulfonylurea therapy on plasma lipids and high-density lipoprotein composition, 11 obese diabetic Pima Indians with type II, or non-insulin-dependent, diabetes mellitus were studied before and after tolazamide therapy for one month. Diet composition and weight were kept constant, and the data were compared with a control group of 18 age-, sex-, and weight-matched non-diabetic subjects. Improvement of glycemic control was accompanied by significant decreases in total and very-low-density lipoprotein triglycerides. Total and low-density lipoprotein cholesterol also declined significantly, and there was an increase in the ratio of high-density lipoprotein to low-density lipoprotein cholesterol. Concentrations of total high-density lipoprotein cholesterol, phospholipid, and apolipoprotein AI were unchanged. An increase in the proportion of the high-density lipoprotein 2 subfraction, however, was suggested by significant increases in the ratios of high-density lipoprotein 2 to high-density lipoprotein 3 cholesterol and apolipoprotein AI. There was also a change in the composition of the high-density lipoprotein 2 particle, as indicated by changes in the molar ratio of cholesterol to apolipoprotein AI. The data suggest that improvement of glycemic control after sulfonylurea therapy, when weight and diet composition remain constant, reverses several of the lipoprotein abnormalities observed in type II diabetic patients. There was no evidence of changes in lipoproteins in directions associated with an increased risk for atherosclerosis.

Adipose Tissue↗
PubMed1985

Sequence of alcohol-induced initial changes in plasma lipoproteins (VLDL and HDL) and lipolytic enzymes in humans.

The sequence of alterations in the concentration and composition of different plasma lipoproteins following alcohol intake is not known. We therefore monitored the concentrations of cholesterol, triglycerides, phospholipids, and proteins in the major lipoprotein fractions (VLDL, LDL, HDL2, and HDL3) in ten nonalcoholic healthy male volunteers who were given 5.5 g of alcohol per kilogram of body weight during 21/2 days (a weekend). In addition, lipoprotein lipase activity was measured in post-heparin plasma and in adipose tissue and hepatic lipase activity was measured in post-heparin plasma before and after the experiment. in a separate control experiment, the same subjects received meals and liquids without alcohol. Blood alcohol levels remained below 1.5 g/L. Alcohol caused a progressive increase in the fasting VLDL triglyceride and phospholipid concentrations, both of which were doubled during the experiment (P less than 0.001). In contrast, the VLDL cholesterol levels remained unchanged until the third morning, when there was a slight increase. The LDL triglyceride and phospholipid concentrations also rose without simultaneous changes in the LDL cholesterol concentration. Consistent with these changes, the HDL cholesterol concentration showed no response to alcohol during the experiment, but the HDL phospholipid level rose from 76 to 99 mg/dL (P less than 0.001). This was reflected as an increase in the HDL2 concentration from 124 to 158 mg/dL (P less than 0.01), whereas no change occurred in the HDL3 level. The increment of HDL2 concentration was due to a rise of its triglycerides, phospholipids, and apoproteins A-I and A-II but not to a rise of cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1985

Multiple disturbances of free fatty acid metabolism in noninsulin-dependent diabetes. Effect of oral hypoglycemic therapy.

To assess the mechanisms for the elevation of free fatty acids in noninsulin-dependent diabetes, free fatty acid metabolism and lipid and carbohydrate oxidation were compared in 14 obese diabetic Pima Indians and in 13 age-, sex-, and weight-matched nondiabetics. The studies were repeated in 10 of the diabetics after 1 mo of oral hypoglycemic therapy. Fasting plasma glucose concentrations were elevated in diabetics (242 +/- 14 vs. 97 +/- 3 mg/dl, P less than 0.01) and decreased to 142 +/- 12 (P less than 0.01) after therapy. Fasting free fatty acid concentrations were elevated in diabetics (477 +/- 26 vs. 390 +/- 39 mumol/liter, P less than 0.01) and declined to normal values after therapy (336 +/- 32, P less than 0.01). Although free fatty acid transport rate was correlated with obesity (r = 0.75, P less than 0.001), the transport of free fatty acid was not higher in diabetics than in nondiabetics and did not change after therapy. On the other hand, the fractional catabolic rate for free fatty acid was significantly lower in untreated diabetics (0.55 +/- 0.04 vs. 0.71 +/- 0.06 min-1, P less than 0.05); it increased after therapy to 0.80 +/- 0.09 min-1, P less than 0.05, and was inversely correlated with fasting glucose (r = -0.52, P less than 0.01). In diabetics after therapy, lipid oxidation rates fell significantly (from 1.35 +/- 0.06 to 1.05 +/- 0.01 mg/min per kg fat-free mass, P less than 0.01), whereas carbohydrate oxidation increased (from 1.21 +/- 0.10 to 1.73 +/- 0.13 mg/min per kg fat-free mass, P less than 0.01); changes in lipid and carbohydrate oxidation were correlated (r = 0.72, P less than 0.02), and in all subjects lipid oxidation accounted for only approximately 40% of free fatty acid transport. The data suggest that in noninsulin-dependent diabetics, although free fatty acid production may be elevated because of obesity, the elevations in plasma free fatty acid concentrations are also a result of reduced removal, and fractional clearance of free fatty acid appears to be closely related to diabetic control. Furthermore, the increase in fractional clearance rate, despite a marked decrease in lipid oxidation, suggests that the clearance defect in the diabetics is due to an impairment in reesterification, which is restored after therapy.

Adult↗
PubMed1985

Glycemic control and serum lipoproteins after total pancreatectomy.

Carbohydrate and lipid metabolism were studied in 10 patients who had undergone total pancreatectomy. The results were compared with Type I diabetic patients and normal subjects, all of whom were matched for age, sex and weight. At the same level of glycemic control, the daily need for insulin was significantly lower in the patients with pancreatogenic diabetes than in those with Type I diabetes. Concentrations of serum total VLDL and HDL triglyceride were higher in the pancreatectomized patients than in the diabetic or normal controls, whereas concentrations of serum total and LDL cholesterol were significantly lower. The composition of the VLDL, LDL and HDL particles was abnormal in the totally pancreatectomized patients as all three lipoprotein fractions were enriched in triglyceride. HDL2 cholesterol was similar in the totally pancreatectomized patients to that in the other two groups but HDL3 cholesterol was lower. Postheparin plasma lipoprotein lipase and hepatic lipase activities were normal. It is concluded that in totally pancreatectomized patients the changes in the lipoprotein profile on reflect more the action of various confounding factors, i.e. malabsorption, continuance of alcohol abuse and dietary changes than the impact of the diabetes itself.

Adult↗
PubMed1984

Response of adipose tissue lipoprotein lipase activity and serum lipoproteins to acute hyperinsulinaemia in man.

In order to assess the short-term effects of hyperinsulinaemia and hyperglycaemia on adipose tissue lipoprotein lipase activity and on serum lipoproteins, we measured these variables in ten normal subjects during euglycaemic and hyperglycaemic hyperinsulinaemic clamps. The mean steady-state plasma glucose and insulin concentrations, respectively, were 4.7 mmol/l and 101 mU/l during euglycaemic moderate-insulin clamp, 4.9 mmol/l and 565 mU/l during euglycaemic high-insulin clamp, and 8.8 mmol/l and 148 mU/l during hyperglycaemic clamp. Saline infusion was used as control. The adipose tissue lipoprotein lipase activity rose significantly over 5 h during high-insulin clamp (p less than 0.01) and during hyperglycaemic clamp (p less than 0.05), but did not change during the moderate-insulin clamp. The magnitude of change of lipoprotein lipase activity from baseline (either rise or fall) was inversely related to the preclamp activity during euglycaemic moderate-insulin clamp (r = -0.67), during hyperglycaemic clamp (r = -0.68) and during infusion of saline (r = -0.75, p less than 0.05). Total serum triglyceride concentration decreased significantly during all clamp studies compared with the control experiment. This change was mainly accounted for by a decrease of VLDL triglyceride. The LDL cholesterol level fell by an average of 5% (p less than 0.05) during the high-insulin clamp and by 10% (p less than 0.05) during the hyperglycaemic clamp. The HDL cholesterol level did not change significantly. It is concluded that adipose tissue lipoprotein lipase activity in man is increased by physiological insulin levels during hyperglycaemia and also by supraphysiological insulin levels during euglycaemia, but is not influenced by physiological hyperinsulinaemia without hyperglycaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1984

Glucose tolerance, plasma lipoproteins and tissue lipoprotein lipase activities in body builders.

Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118 +/- 4%), eight weight-matched (RBW 120 +/- 5%) and seven normal-weight controls (RBW 111 +/- 3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P less than 0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P less than 0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and VO2max. Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL2 and HDL3 cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users. A possible mechanism for the up-regulation of high density lipoprotein by ethanol.

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased (P less than 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (HDL2 and HDL3) cholesterol fell. The per cent decrease in HDL2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate (r = +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.

Adult↗
PubMed1984

Postheparin plasma lipase activities and plasma lipoproteins in newborn infants.

We measured blood glucose, serum insulin and apoprotein A-I and A-II, and triglycerides and cholesterol contained in serum lipoprotein fractions of 24 full-term newborn infants who underwent exchange transfusion with heparinized blood for hematological reasons. The values were similar to those previously reported for healthy newborn infants. We also measure lipoprotein and hepatic lipase activities with specific methods. Fifteen minutes after an intravenous heparin bolus of 100 IU/kg, mean lipoprotein lipase activity in infants (16.0 mumol free fatty acids/ml/h) was as in adults. In contrast, hepatic lipase activity was significantly higher in infants (54.3 mumol free fatty acids/ml/h) than in adults. There was no sex difference in the infant lipase activities. Lipoprotein and hepatic lipase activities were also measured 5 and 15 min after a heparin bolus of 10 and 50 IU/kg: 10 IU/kg released only part of the lipase activities. In addition, the two lipases were measured during the exchange transfusion. Although 92% of the original infant blood was removed, lipoprotein lipase activity remained constant. In contrast, hepatic lipase activity decreased considerably. In infants, postheparin lipolytic activity is a conventional measure of lipoprotein lipase. Lipoprotein and hepatic lipases comprise 95% of postheparin lipolytic activity. In our infants, hepatic lipase activity was 3.4 times higher than lipoprotein lipase activity. Hence, it seems unjustified to use postheparin lipolytic activity as a measure of lipoprotein lipase.

Cholesterol↗
PubMed1984

Postheparin plasma lipoprotein and hepatic lipases in preterm neonates.

Postheparin plasma lipoprotein lipase and hepatic lipase activities of 11 preterm infants aged 1 to 4 days were measured 15 min after a heparin bolus of 100 IU/kg and during an exchange transfusion performed with fresh heparinized blood. Each infant had a birth weight (range, 1210-3490 g) appropriate for gestational age (range, 28-36 (wk). Eight of the infants (group 1) were in good clinical condition while three (group 2) suffered from septic shock. After the heparin bolus and during the exchange transfusion, lipoprotein and hepatic lipase activities in group 1 were higher than in term infants. In group 2, both lipase activities were extremely low after the heparin bolus but increased approaching the activities of group 1 during the exchange transfusion. Clearance of fat from the circulation is slower in preterm than term infants. This has been attributed to low lipoprotein lipase activity. Our results, however, indicate that lipoprotein lipase is not the reason for slow clearance of fat from the circulation in preterm infants except in septic shock.

Blood Group Incompatibility↗
PubMed1984

Site of insulin resistance in type 1 diabetes: insulin-mediated glucose disposal in vivo in relation to insulin binding and action in adipocytes in vitro.

To evaluate the mechanism of insulin resistance in type 1 diabetes mellitus, we measured insulin sensitivity in vivo and insulin action in adipocytes in vitro. The study groups consisted of 18 insulin-treated type 1 diabetic patients and 14 matched normal subjects. In each subject, insulin-mediated glucose disposal in vivo was measured by the euglycemic clamp technique. An open surgical biopsy was performed in 9 diabetic and 7 healthy subjects to obtain abdominal sc adipose tissue for the measurement of [125I]insulin binding, D-[14C]-glucose transport, oxidation, and lipogenesis. During the euglycemic clamp studies, similar steady state plasma glucose (4.8 mmol/liter) and insulin (80 mU/liter = 700 pM) levels were maintained in both groups. The rate of glucose metabolism (M) was 43% lower in the diabetic patients (4.75 +/- 0.34 mg/kg X min) than in the normal subjects (8.27 +/- 0.43 mg/kg X min; P less than 0.001). [125I]Insulin binding to adipocytes was reduced in the diabetic patients (26% reduction in tracer binding; P less than 0.05) due to a reduction in receptor number. Insulin binding was not related to the M value at any insulin concentration. Basal and insulin-stimulated rates of glucose transport were not significantly different in diabetic and normal subjects. The basal glucose oxidation rate was reduced by 50% (P less than 0.02), and maximal glucose oxidation was reduced by 49% (P less than 0.03) in the diabetic patients (237 +/- 30 vs. 359 +/- 49 pmol/30,000 cells X 90 min, basal vs. maximal glucose oxidation, respectively) compared to those in normal subjects (513 +/- 101 vs. 700 +/- 133 pmol/30,000 cells X 90 min). The percentage responses of glucose oxidation and glucose transport to insulin were similar in both groups. Glucose oxidation rates at basal (r = 0.68; P less than 0.01), half-maximally (ED50; r = 0.70; P less than 0.01), and maximally (r = 0.64; P less than 0.05) effective insulin concentrations were positively related to the M value. Basal and insulin-stimulated rates of lipogenesis were comparable between the diabetic and normal subjects. In conclusion, insulin-mediated glucose disposal in vivo is reduced in conventionally treated type 1 diabetic patients. In vitro, adipocytes from diabetes bound slightly less insulin at tracer insulin concentrations, but the magnitude of this reduction was not related to impairment of glucose metabolism in vivo. Of the pathways of glucose metabolism studied, the rate of glucose oxidation was most affected. A significant relationship was found between the M value and the rate of in vitro glucose oxidation.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1983

Plasma lipoproteins, lipolytic enzymes, and very low density lipoprotein triglyceride turnover in Cushing's syndrome.

Plasma lipoproteins, triglyceride turnover, and lipolytic enzymes were measured in 11 women with Cushing's syndrome. The studies were repeated 3 and 12 months after surgical treatment. Eleven healthy women of similar age and relative body weight served as controls. Before treatment the mean values of total cholesterol and triglyceride, of very low-density lipoprotein (VLDL) triglyceride and cholesterol, low density lipoprotein triglyceride and cholesterol, and high density lipoprotein cholesterol were all significantly increased in the patients with Cushing's syndrome. The triglyceride levels were only moderately elevated, the highest values being found in patients with adrenocortical adenoma. The production rate of VLDL triglyceride was higher in patients (13.2 mg/h . kg) than in controls (9.5 mg/h . kg, P less than 0.05), whereas the fractional catabolic rate of VLDL triglyceride was not significantly different. Consistent with the latter finding, the lipoprotein lipase activities of adipose tissue, skeletal muscle, and postheparin plasma were similar in patients and controls. The postheparin plasma hepatic lipase activity of the patients was at the lower end of the normal range. All lipid and lipoprotein abnormalities were completely abolished after successful surgery. It is concluded that endogenous hypercortisolism stimulates the hepatic production of VLDL particles. The effect is probably based on multifactorial mechanisms. In the presence of unchanged removal this leads to elevated levels of VLDL, low density lipoprotein, and high density lipoprotein.

Adult↗
PubMed1983

No evidence of amyloidosis in type I diabetics treated with continuous subcutaneous insulin infusion.

A recent study has demonstrated secondary amyloidosis in dogs treated with continuous intravenous insulin infusion. Since elevated levels of serum amyloid A protein (SAA) and diminished amyloid fibril degrading activity (AFDA) are associated with amyloidosis, we measured SAA and AFDA in ten type I diabetics treated with continuous subcutaneous insulin infusion and in five conventionally treated patients. Only one pump- and one conventionally treated patient had detectable but low SAA levels, comparable with these seen in healthy controls. In patients with secondary amyloidosis the mean SAA level was 24-fold higher than in controls (P less than 0.001). Similarly, in both diabetic groups, AFDA was normal whereas it was reduced by 41% in patients with amyloidosis (P less than 0.001). Furthermore, no local amyloidosis was seen at the infusion site in any of the patients studied. Thus, our data fail to provide any evidence of secondary amyloidosis in patients treated for 3-40 mo with continuous subcutaneous insulin infusion.

Adult↗
PubMed1982

Human postheparin plasma hepatic lipase activity against triacylglycerol and phospholipid substrates.

Recent evidence has suggested that the major physiological substrate of the heparin-releasable (postheparin plasma) hepatic lipase is HDL2-phospholipid. However, all the current assay methods for this enzyme are based on the use of triacylglycerol substrate. Even though both lipolytic activities of hepatic lipase are likely to be due to a single enzyme it is possible that the use of unphysiological lipid as a substrate may give misleading results. Therefore we did parallel assays of the activity of postheparin plasma hepatic lipase using triacylglycerol, monoacylglycerol and phospholipid substrates. The correlation coefficients between the three lipolytic activities were 0.95-0.98, indicating that identical results are obtained using any of these three lipids in the assay of postheparin plasma hepatic lipase.

Glycerides↗
PubMed1982

Lipoprotein lipase activity and serum lipoproteins in untreated type 2 (insulin-independent) diabetes associated with obesity.

Serum lipoproteins and the heparin-releasable lipoprotein lipase (LPL) activity of adipose tissue and skeletal muscle were measured in 36 untreated obese patients with Type 2 (insulin-independent) diabetes and the values were compared with those of non-diabetic subjects of similar age, sex and relative body weight. In diabetic men, the LPL activity of adipose tissue was significantly reduced when expressed per tissue weight or per fat cell (p less than 0.01). Diabetic females had slightly but not significantly lower LPL activity in adipose tissue than the non-diabetic females. The muscle LPL activity was similar in diabetic and non-diabetic subjects of both sexes. When the diabetic men were classified according to fasting blood glucose, the patients with high glucose levels had lower adipose tissue LPL activity than those with moderate hyperglycemia. In both diabetic and non-diabetic subjects, there was a significant positive correlation between HDL cholesterol concentrations and adipose tissue LPL activity. It is concluded that Type 2 diabetes influences adipose tissue LPL activity and plasma lipoprotein concentrations and that this effect is superimposed on the similar changes produced by obesity alone.

Adult↗
PubMed1982

In vitro catabolism of human plasma very low density lipoproteins. Effects of VLDL concentration on the interconversion of high density lipoprotein subfractions.

The effect of lipolysis of human plasma very low density lipoproteins (VLDL) on the distribution of high density lipoprotein subfractions was studied in an in vitro system consisting of purified bovine milk lipoprotein lipase and albumin. The distribution of lipids and apoproteins (apoC-II and apoC-III) within the lipoprotein fractions corresponding to HDL2 (d = 1.063-1.120 g/ml) and HDL3 (d = 1.120-1.210 g/ml) was dependent upon the concentration of VLDL in the incubation mixture. After lipolysis of an incubation mixture containing VLDL-triglyceride (0.6 mg triglyceride/ml) and HDL3 (0.1 mg protein/ml), most of the lipid and apoproteins were recovered in HDL3. At higher concentrations of VLDL-triglyceride relative to HDL3-protein (1.8 or 2.4 mg of VLDL-triglyceride and 0.1 mg of HDL3-protein) the amount of lipid and apoprotein isolated in the HDL3 density fraction decreased after lipolysis and there was an increase in the amount isolated between d 1.063-1.120 g/ml. These results provide additional evidence for the conversion of HDL3 to HDL2 during lipolysis. Furthermore, they suggest that the relative distribution of plasma HDL2 and HDL3 is related to the rate of catabolism of triglyceride-rich lipoproteins.

Animals↗