Search PubMed⌕ Search

Biomedical subjects

M R Taskinen

Publications and source records attributed to M R Taskinen.

At least 19 recordsLinked to original sources
PubMed1992

A novel polymorphism of apolipoprotein A-IV is the result of an asparagine to serine substitution at residue 127.

We have identified a hitherto unknown genetic polymorphism of apolipoprotein A-IV (apoA-IV). The molecular basis for this polymorphism is an A to G substitution at nucleotide 1687 resulting in an Asn to Ser change of amino acid 127. The frequencies of the two apoA-IV alleles (designated apoA-IV127Asn and apoA-IV127Ser), determined by Hin c II restriction analysis of PCR amplified exon three of the apoA-IV gene, were 0.788 and 0.212, respectively, in a Finnish population sample. Allele frequencies of another polymorphism due to a Thr to Ser substitution at amino acid 347 were determined using Hinf I restriction analysis. The allele frequencies were 0.823 for apoA-IV347Thr and 0.177 for apoA-IV347Ser. None of the apoA-IV polymorphisms (apoA-IV127:Asn----Ser, apoA-IV347:Thr----Ser and apoA-IV360:Gln----His) had any effect on plasma lipid and lipoprotein concentrations in cohorts of dyslipidemic men and in a population sample of normolipidemic controls. There was also no association between the history of previous myocardial infarction and any of the apoA-IV alleles.

Alleles↗
PubMed1992

Metabolism of HDL apolipoprotein A-I and A-II in type 1 (insulin-dependent) diabetes mellitus.

Concentrations of HDL cholesterol and apolipoprotein A-I are commonly increased in Type 1 (insulin-dependent) diabetes mellitus but the mechanisms whereby diabetes influences HDL metabolism have not been studied. We investigated the metabolism of HDL apoproteins A-I and II in normolipidaemic Type 1 diabetic men (n = 17, HbA1 6.4-11.9%) without microalbuminuria but with a wide range of HDL cholesterol (0.85-2.10 mmol/l) and in nondiabetic men (n = 18) matched for body mass index and the range of HDL cholesterol. Input rates and fractional catabolic rates for apolipoproteins A-I and II were determined following injection of 125I-apolipoprotein A-I and 131I-apolipoprotein A-II tracers. Additional multicompartmental analysis was performed using a model to describe the kinetics of HDL particles containing only apolipoprotein A-I (Lp A-I) and apolipoprotein A-I and apolipoprotein A-II (Lp A-I/A-II). No gross differences from normal subjects were observed in the mean levels of lipids, lipoproteins, apoproteins and the lipolytic enzymes in the diabetic men as a result of the selection process. Furthermore, the relationship between apolipoprotein A kinetics and plasma HDL cholesterol levels appeared to be preserved in the diabetic group. However, some normal interrelationships were disrupted in the diabetic men. Firstly, the rate of apolipoprotein A-II synthesis was 22% lower than in control subjects (p less than 0.05). Modelling indicated that this was due to decreased input of Lp A-I/A-II particles whereas the input of Lp A-I particles was similar in the two groups. Secondly, there was no correlation between VLDL triglyceride and HDL cholesterol or VLDL triglyceride and the fractional catabolic rate of apolipoproteins A-I and A-II in diabetic men in contrast to that seen in control subjects. We conclude that there is a disruption in the normal association between VLDL and HDL metabolism in Type 1 diabetic men and postulate that the observed differences may be due to the therapeutic use of exogenous insulin.

Adult↗
PubMed1992

Effects of interferon alpha on insulin binding and glucose transport in human adipocytes.

We have previously demonstrated that interferon administration impairs glucose tolerance and causes insulin resistance in healthy man. Whether this is a direct effect of interferon is not known. The present study was undertaken to examine directly the effect of interferon alpha on insulin binding and action on glucose transport in isolated human adipocytes. Different concentrations of interferon alpha (range 10(-3)-10(5) IU ml-1) and different incubation times (0-5-24 h) with interferon were employed. Acute and 5-h and 24-h exposure of human adipocytes to 10(-2)-10 IU ml-1 of interferon increased the high affinity binding of 125I-insulin (P less than 0.05). In contrast, human interferon alpha had no effect on insulin binding in rat adipocytes. In short-term studies interferon had no effect on 14C-glucose transport clearance. 24-h preincubation of human adipocytes with 10(-2), 10, 10(4) IU ml-1 interferon increased maximally-insulin stimulated 14C-glucose transport clearance (P less than 0.05) and glucose transport responsiveness to insulin was enhanced by 24% (P less than 0.05) in cells exposed to 10(-2) IU ml-1 interferon. After 5 and 24-h preincubations with interferon we observed modest changes in glucose transport sensitivity to moderate concentrations of insulin (50-100 pM) with upregulation in the presence of 10(-2)-10 IU ml-1 interferon and downregulation in the presence of 10(4)-10(5) IUm ml-1 interferon (P less than 0.05). The insulin sensitivity index (ED50) did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

One-year response to evening insulin therapy in non-insulin-dependent diabetes.

We studied the 1-year response and predictors of the response to combination therapy with evening insulin and oral agents in NIDDM patients with a secondary failure. Injection of intermediate-acting (Monotard HM) or long-acting (Ultratard HM) insulin was added to previous oral therapy in 17 diabetics (of mean age (+/- SD) 54 +/- 2 years, BMI 27.6 +/- 0.5 kg m-2). The initial insulin dose was in the range 10-16 U, and the mean dose was 23 +/- 2 U d-1 at 12 months. During the year, combination therapy reduced the mean fasting blood glucose concentration (12.7 +/- 0.6 vs. 8.4 +/- 0.7 mmol l-1, P less than 0.001) and HbA1 (10.7 +/- 0.3 vs. 9.8 +/- 0.4%, P less than 0.01). Body weight increased by 4.4 +/- 0.7 kg (P less than 0.001). The serum cholesterol concentration decreased by 14% (P less than 0.01), but serum triglyceride and HDL-cholesterol levels remained unchanged. Elevation of serum triglycerides and plasma free fatty acids (FFAs) at baseline predicted a poor long-term outcome to this mode of therapy. In conclusion, the addition of evening injections of insulin to oral therapy improves glycaemic control in poorly controlled NIDDM patients. However, initial hypertriglyceridaemia predicts a poor long-term outcome to evening insulin supplementation.

Adult↗
PubMed1992

Increased volume of gastric contents in diabetic patients undergoing renal transplantation: lack of effect with cisapride.

Gastroparesis is a frequently unrecognized complication of insulin-dependent diabetes mellitus, which subjects these patients to the risk of aspiration at induction of anaesthesia. The effect of oral cisapride on volume and pH of gastric contents was studied in 24 diabetic and 24 non-diabetic uraemic patients undergoing renal transplantation. All patients were allocated randomly in a double-blind fashion to receive either 10 mg of cisapride or placebo orally approximately 100 min before anaesthesia and three times daily for the first 2 postoperative days. After the induction of anaesthesia, gastric contents were aspirated through a nasogastric tube, and the pH and volume were measured. The emptiness of the stomach was verified by gastroscopy. Gastric volumes exceeding 0.4 ml.kg-1 were observed in 12/24 of the diabetic and 4/24 of the non-diabetic uraemic patients (P < 0.01). The pH of the gastric contents did not differ between the groups, ranging from 1-8 in diabetics and 1-7 in non-diabetics. Cisapride lacked effect on gastric contents and postoperative gastrointestinal motility. Diabetic uraemic patients had larger gastric volumes than their non-diabetic controls at induction of anaesthesia. Cisapride had no effect on gastric emptying preoperatively nor on postoperative bowel function.

Administration, Oral↗
PubMed1992

Lipoproteins and their genetic variation in subjects with and without angiographically verified coronary artery disease.

To examine the concentration of serum lipoproteins and the association of their genetic variation with the occurrence of coronary artery disease (CAD), composite serum lipoprotein profiles including lipoprotein(a) (Lp[a]), apolipoprotein (apo) E phenotypes, and apo B Xba I genotypes were determined in patients with angiographically verified CAD (CAD+ group, n = 111) and in subjects with no angiographic evidence of CAD (CAD- group, n = 46). In addition, we determined the concentrations of serum lipids, lipoproteins, and apolipoproteins in 96 healthy controls. Both CAD- and CAD+ groups had lower concentrations of apos A-I and A-II but higher concentrations of serum total and very low density lipoprotein triglyceride and very low density lipoprotein cholesterol than did healthy controls. The mean concentrations of serum total and low density lipoprotein cholesterol and the median values of Lp(a) were similar in the CAD+ and CAD- groups, both having higher concentrations of low density lipoprotein cholesterol and apo B than the healthy controls. Irrespective of gender, patients with CAD had significantly lower serum high density lipoprotein cholesterol than did those without CAD (1.48 +/- 0.40 versus 1.16 +/- 0.29 mmol/l, p less than 0.001). In women, the mean serum total and very low density lipoprotein triglyceride concentration was also higher in the CAD+ than in the CAD- group. The frequency of the apo E4 allele (epsilon 4) was significantly higher in the CAD+ group (0.293) than in the CAD- group (0.174; p less than 0.001). The frequencies of the two apo B alleles, X1 (Xba I restriction site absent) and X2 (Xba I restriction site present), were similar in the two groups. Stepwise discriminant analysis revealed that in men, serum high density lipoprotein cholesterol had the highest power to discriminate for CAD. In addition, the concentration of plasma apo B levels and the occurrence of apo E phenotypes were independently associated with CAD in men. In women, the only independent factor associated with CAD after adjustment for beta-blocker and diuretics usage was the concentration of serum triglycerides.

Adult↗
PubMed1992

Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus.

In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein pattern is antiatherogenic in individuals with IDDM who are treated and have optimal glycemic control. In contrast, NIDDM is associated with atherogenic changes of serum lipids and lipoproteins regardless of the mode of treatment. In people with both types of diabetes, the distribution of apoE phenotype seems to be similar to that in nondiabetic populations. IDDM patients with microalbuminuria show atherogenic changes of lipoproteins and have elevated levels of Lp(a), which is a risk factor of coronary artery disease. Whether glycemic control influences the concentration of Lp(a) is still an open question. An important issue is that the concentration of a lipoprotein can be normal without excluding compositional abnormalities that are potentially atherogenic. Such alterations are present in people with both IDDM and NIDDM. Consequently, it has been questioned whether the target values to start treatment should be lower in diabetic than in nondiabetic populations.

Diabetes Complications↗
PubMed1992

Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis.

Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients.

Apoproteins↗
PubMed1992

Abnormalities of low density lipoproteins in normolipidemic type II diabetic and nondiabetic patients with coronary artery disease.

The characteristics of low density lipoproteins (LDL) of ten non-insulin-dependent diabetic (NIDDM) and ten nondiabetic patients with coronary artery disease (CAD) were investigated and compared to LDL of ten NIDDM patients without CAD and ten healthy persons. All subjects had LDL cholesterol below 160 mg/dl and serum triglycerides below 200 mg/dl. The mean LDL particle size and particle distribution profiles were analyzed by using nondenaturing polyacrylamide gradient gel electrophoresis. The LDL composition and hydrated density distribution were investigated by using density gradient ultracentrifugation. Both NIDDM and nondiabetic CAD patients tended to have larger LDL particles than NIDDM patients without CAD and healthy subjects. The increase of LDL particle size of CAD patients was due to marked enrichment of triglycerides (TG) in their LDL. The percentage content of TG in LDL of NIDDM patients with CAD was 14.5% and in LDL of nondiabetic CAD patients 13.4% compared with 7.9% in LDL of NIDDM patients without CAD and 7.2% in normal-LDL (P less than 0.05 or less between either CAD group and NIDDM without CAD or normals). The LDL TG/apolipoprotein (apo) B weight ratio was significantly higher in both CAD groups compared with LDL of the two groups without CAD (0.70 and 0.68 vs. 0.38 and 0.34, respectively, P less than 0.05, P less than 0.05 and P less than 0.01, P less than 0.01). The LDL total lipid to apoB weight ratio was similar in all four groups. Consistent with this, the hydrated density distributions of LDL in the four groups were similar, the average peak densities being 1.0346 g/ml, 1.0331 g/ml, 1.0331 g/ml, and 1.0331 g/ml, respectively. The findings of this study demonstrate that normolipidemic patients with CAD may have marked abnormalities in th eir LDL composition and these anomalies are present in both diabetic and nondiabetic patients.

Adult↗
PubMed1991

Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease.

We determined TaqI-A, TaqI-B and EcoNI genotypes at the cholesteryl ester transfer protein (CETP) locus in 111 healthy volunteers and in 187 hyperlipidemic men of whom 72 had suffered a myocardial infarction. There were no significant differences in the allele distributions at these polymorphic loci either between the population sample and the hyperlipidemic subjects, or between patients with and without previous myocardial infarction. To detect the associations between the CETP polymorphisms and serum lipid and apoprotein levels, we determined the serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol, apoA-I, apoA-II and apoB in the subjects studied and correlated them to the 3 RFLPs. No significant differences were observed in the serum levels of apoproteins and lipid parameters between subjects with different genotypes in any of these polymorphic CETP loci, either in the population sample or in hyperlipidemic men. Multivariate analyses did not reveal a significant independent role for any of the 3 polymorphisms in determining serum HDL-cholesterol or apoA-I levels after adjusting for triglyceride and low density lipoprotein cholesterol concentrations. This was evident for the group of healthy volunteers and for hyperlipidemic subjects, including those who had survived a myocardial infarction. We conclude that, in Finns, the CETP RFLPs are not useful markers for the risk of coronary heart disease.

Adult↗
PubMed1991

Modulation of hepatic glucose production by non-esterified fatty acids in type 2 (non-insulin-dependent) diabetes mellitus.

To study the effect of changes in plasma non-esterified fatty acid concentration on suppression of hepatic glucose production by insulin eight Type 2 (non-insulin-dependent) diabetic patients participated in three euglycaemic, hyperinsulinaemic (108pmol.m2-1.min-1) clamp studies combined with indirect calorimetry and infusion of [3-3H]-glucose and [1-14C]palmitate; (1) a control experiment with infusion of NaCl 154 mmol/l, (2) heparin was infused together with insulin, and (3) an antilipolytic agent, Acipimox, was administered at the beginning of the experiment. Six healthy volunteers participated in the control experiment. Plasma non-esterified fatty acid concentrations during the insulin clamp were in diabetic patients: (1) 151 +/- 36 mumol/l, (2) 949 +/- 178 mumol/l, and (3) 65 +/- 9 mumol/l; in healthy control subjects 93 +/- 13 mumol/l. Non-esterified fatty acid transport rate, oxidation and non-oxidative metabolism were significantly higher during the heparin than during the Acipimox experiment (p less than 0.001). Suppression of hepatic glucose production by insulin was impaired in the diabetic compared to control subjects (255 +/- 42 vs 51 +/- 29 mumol/min, p less than 0.01). Infusion of heparin did not affect the suppression of hepatic glucose production by insulin (231 +/- 49 mumol/min), whereas Acipimox significantly enhanced the suppression (21 +/- 53 mumol/min, p less than 0.001 vs 154 mmol/l NaCl experiment). We conclude that insulin-mediated suppression of hepatic glucose production is not affected by increased non-esterified fatty acid availability. In contrast, decreased non-esterified fatty acid availability enhances the suppression of hepatic glucose production by insulin.

Administration, Oral↗
PubMed1991

The effect of moderate alcohol intake on serum apolipoprotein A-I-containing lipoproteins and lipoprotein (a).

Two main types of lipoprotein particles are identified within high-density lipoprotein (HDL): those containing both apolipoprotein (apo) A-I and apo A-II (Lp A-I:A-II) and those containing only apo A-I (Lp A-I). To study the effects of prolonged moderate alcohol intake on apo A-I-containing lipoproteins in serum, 60 g/d of ethanol was administered to 10 healthy male volunteers (age, 27 to 45 years) during 3 weeks. The drinking period was preceded and followed by an abstinence period of 3 weeks. The HDL3 cholesterol level increased by 17% (P less than .01) and decreased by 22% (P less than .001) on and off alcohol, respectively. The HDL2 cholesterol increased by 17% (P = NS) during ethanol intake and decreased by 14% during the following abstention (P less than .01). The serum concentration of apo A-I increased by 17% (P less than .001) during drinking and came back to the starting level after 2 weeks of abstention. Ethanol intake caused an increase in the serum levels of both Lp A-I and Lp A-I:A-II, the former explaining one third of the total increase of apo A-I. The Lp (a) concentration decreased by 33% (P less than .05) during the first week of ethanol intake, but increased back to the starting level until the end of drinking. These data suggest that the increment of the antiatherogenic Lp A-I may be one beneficial effect provided by ethanol with respect to coronary heart disease.

Adult↗
PubMed1991

Effects of continuous insulin infusion therapy on lipoprotein surface and core lipid composition in insulin-dependent diabetes mellitus.

To determine whether intensive insulin therapy has the same beneficial effects on lipoprotein composition that it has been shown to have in insulin-dependent diabetes mellitus (IDDM) on the routinely measured plasma lipids, we studied 10 patients after 6 months of conventional therapy (CIT) and again after 6 months of therapy with continuous subcutaneous insulin infusion (CSII). While the mean of home blood glucose levels (8.1 +/- 0.5 v 7.9 +/- 0.5 mmol/L) decreased no further, plasma triglycerides (TG) (CIT, 102.7 +/- 25.0; CSII, 89.6 +/- 27.1 mg/dL; P less than .001) decreased after CSII, and high-density lipoprotein cholesterol (HDL-C) increased significantly, primarily as a consequence of an increase in HDL2 (CIT, 12.2 +/- 6.0; CSII, 18.1 +/- 6.3 mg/dL; P less than .02). Low-density lipoprotein cholesterol (LDL-C) was unchanged (CIT, 82.2 +/- 32; CSII, 84.0 +/- 27.8 mg/dL). After CIT, two indices of lipoprotein surface composition were altered: (1) the free cholesterol (FC) to lecithin ratio, which is a new cardiovascular risk factor, was abnormally increased in plasma, very-low-density lipoprotein (VLDL) + LDL, and HDL, and (2) the sphingomyelin to lecithin ratio, an index of the surface rigidity of lipoproteins, was increased in the HDL subfractions. While CSII treatment resulted in favorable changes in whole plasma lipids, it failed to correct these disturbances in composition. Since the participation of lipoproteins in certain steps in reverse cholesterol transport appears to be impaired when their surface constituents are altered, persistence of these disturbances may sustain the increased cardiovascular risk of IDDM patients, even when their clinical control is very good and their plasma lipids are normal.

Adult↗
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↗