Biomedical subjects

M R Taskinen

Publications and source records attributed to M R Taskinen.

At least 55 records · Page 3Linked to original sources

PubMed1994

Abnormal metabolism of postprandial lipoproteins in patients with non-insulin-dependent diabetes mellitus is not related to coronary artery disease.

To investigate whether abnormalities in alimentary lipemia explain the increased risk of coronary artery disease (CAD) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we performed an oral vitamin A fat-load test in four groups of men (each n = 15): 1) NIDDM and angiographically verified CAD (DM+CAD+): 2) CAD but no diabetes (DM-CAD+); 3) NIDDM but no CAD, excluded by an exercise thallium scan (DM+CAD-); and 4) healthy control subjects (DM-CAD-). The groups were matched for age and body mass index. Plasma obtained after an overnight fast and 2, 3, 4, 6, 9, 12, and 24 h after a fatty meal (78 g fat, 345,000 IU retinyl palmitate [RP]) was separated by density gradient ultracentrifugation into six fractions of triglyceride (TG)-rich lipoproteins: Svedberg flotation units (Sf) > 3200, Sf 1100-3200, Sf 400-1100, Sf 60-400, Sf 20-60, and Sf 12-20. TG, RP, and cholesterol concentrations were measured in plasma and in each lipoprotein fraction. Postprandial plasma TG responses were significantly larger in both NIDDM groups than in the healthy control group. The most marked differences were observed in the Sf 60-400 lipoproteins, whether measured as TG or RP responses. However, there were no differences between the DM+CAD+ and DM+CAD- groups. The between-group differences in alimentary lipemia were only partially explained by fasting TG levels. In contrast to the healthy subjects, no significant negative correlation was observed in the NIDDM patients between alimentary lipemia and lipoprotein lipase activity, implying an abnormality of the lipolysis of TG-rich particles in NIDDM. Levels of atherogenic postprandial remnant lipoproteins are increased in NIDDM. However, in this study the magnitude of alimentary lipemia did not distinguish NIDDM patients with CAD from those without CAD symptoms and normal exercise thallium scans.

Aged↗

PubMed1994

A novel amino acid substitution (His183-->Gln) in exon 5 of the lipoprotein lipase gene results in loss of catalytic activity: phenotypic expression of the mutant gene in a heterozygous state.

We have identified a hitherto unrecognized mutation of the lipoprotein lipase gene (LPL) in a Finnish family with Russian and Swiss ancestors. A single base pair substitution of a guanine for cytosine in codon 183 of exon 5 of the LPL gene results in a change of histidine to glutamine in the mature enzyme protein. Expression of a mutant cDNA construct in COS cells resulted in secretion of inactive LPL enzyme protein confirming the functional significance of the mutation. The proband, a 50-year-old female and her two daughters were all heterozygous for the His183-->Gln mutation. Clinically, the proband was characterized by variable and occasionally severe hypertriglyceridemia, obesity, hypertension, coronary heart disease and non-insulin-dependent diabetes mellitus. The daughters, aged 24 and 19 years, were also obese but had milder hypertriglyceridemia. In conclusion, we have identified a novel LPL mutation that results in the synthesis of an inactive enzyme protein. Although the assessment of a causative link between the mutation and hyperlipidemia awaits further studies, our data suggest that heterozygosity for a functional defect of LPL should be considered in patients presenting with the metabolic dyslipidemic syndrome, "syndrome-X."

Amino Acids↗

PubMed1993

Hyperinsulinism and dyslipidemias as coronary heart disease risk factors in NIDDM.

In conclusion hypertriglyceridemia is accompanied by multiple metabolic disturbances which are potentially atherogenic. Atherogenic pattern of risk factors in insulin resistance syndrome request early intervention to prevent the development of CHD. The practical implication is that the presence of cardiovascular risk factors like hyperinsulinism and dyslipidemias particularly in a person with a family history of NIDDM or hypertension, deserves attention before overt diseases develop. [table: see text]

Coronary Disease↗

PubMed1993

Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in type 2 (non-insulin-dependent) diabetic patients.

Hypertriglyceridaemia and insulin resistance are closely associated but it is unknown whether hypertriglyceridaemia per se contributes to insulin resistance. In the present study we examined whether gemfibrozil, by lowering triglyceride levels, improves the glucoregulatory and antilipolytic action of insulin in Type 2 (non-insulin-dependent) diabetes mellitus. Twenty patients were randomly allocated to receive either placebo or gemfibrozil 1200 mg daily for 12 weeks in a double-blind study. Very low density lipoprotein triglyceride levels decreased in the gemfibrozil group by 42 +/- 12% (p < 0.01). Gemfibrozil had no effect on the diurnal concentration of non-esterified fatty acids (NEFA). At the randomization HbA1c levels were comparable (7.6 +/- 0.3 vs 7.8 +/- 0.2%, NS) and increased slightly both in the gemfibrozil (8.2 +/- 0.4%, p < 0.05) and placebo groups (8.0 +/- 0.3%, NS). Pre- and post-treatment diurnal glucose and insulin concentrations remained unchanged. Basal pre- and post-treatment hepatic glucose production rates were comparable in both groups and similarly suppressed by insulin. Rate of whole body glucose disposal during a low-dose insulin infusion (serum insulin -90 pmol/l) (pre- vs post-gemfibrozil 11.9 +/- 1.1 vs 11.1 +/- 0.7, pre- vs post-placebo 9.9 +/- 1.1 vs 10.8 +/- 0.8 mumol.kg-1.min-1, NS for both) and a high-dose insulin infusion (serum insulin approximately 500 pmol/l) (16.2 +/- 1.7 vs 17.7 +/- 2.7, 17.1 +/- 4.2 vs 17.4 +/- 2.9 mumol.kg-1 x min-1, respectively, NS for both) remained unchanged. Basal pre- and post-treatment NEFA turnover rates were comparable in both groups and similarly suppressed by insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1993

Effect of gemfibrozil on high density lipoprotein subspecies in non-insulin dependent diabetes mellitus. Relations to lipolytic enzymes and to the cholesteryl ester transfer protein activity.

Twenty patients (18 men, 2 women) with non-insulin dependent diabetes mellitus (NIDDM) were randomized to receive either gemfibrozil 1200 mg daily or placebo for 3 months in a double-blind study. The effect of gemfibrozil on plasma HDL subfraction distribution was studied with sequential and density gradient ultracentrifugation and in gradient gel electrophoresis. The concentrations of apo A-I, apo A-II, Lp A-I and Lp A-I:A-II particles were measured. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and plasma cholesteryl ester transfer protein (CETP) activities were also determined. Gemfibrozil increased the concentration of HDL cholesterol (P < 0.01), which was due to the rise of HDL3 cholesterol (+16%), while in the placebo group these values remained unchanged. Gemfibrozil increased the concentrations of apo A-I(+12.6%, NS), apo A-II (+28.2%, P < 0.01) and Lp A-I:A-II particles (+21.6%, P < 0.06) but there were no changes in the placebo group. Neither gemfibrozil nor placebo had any effect on the concentration of Lp A-I particles. As determined by density-gradient ultracentrifugation, gemfibrozil increased the concentration of cholesterol in the most dense HDL fractions (mean density 1.193 g/ml, +22%, P < 0.05 and mean density 1.158 g/ml, +19.3%, P < 0.05). In gradient gel electrophoresis, the gemfibrozil-induced elevations of the cholesterol and protein were most pronounced in the HDL3a (8.8-8.2 nm) region. Gemfibrozil increased LPL and HL activities by 14.7% (P < 0.05) and by 18.8% (P < 0.01), respectively, while in the placebo group LPL and HL activities remained unchanged. Plasma CETP activity was also increased during gemfibrozil treatment while in the placebo group it remained unchanged. We conclude that gemfibrozil causes multiple changes in plasma HDL metabolism. The gemfibrozil-induced elevation of HDL3 and dense HDL subpopulations may reflect the concerted action of LPL, HL and CETP on plasma HDL metabolism.

Apolipoproteins↗

PubMed1993

High density lipoprotein subfractions, apolipoprotein A-I containing lipoproteins, lipoprotein (a), and cholesterol ester transfer protein activity in alcoholic women before and after ethanol withdrawal.

We studied 11 female alcoholics before and after ethanol withdrawal of 2 weeks and 10 healthy normolipidaemic, nonalcoholic women of similar age. In alcoholic women the HDL2 mass was increased by 63% (P < 0.01) on admission and normalized (P < 0.01) during abstention. The concentrations of HDL3 cholesterol and its mass remained unchanged throughout the study. Consistently with the fall of HDL2 gradient gel electrophoresis analyses also demonstrated decrease of the cholesterol concentration of HDL2b and HDL2a (P < 0.05) during alcohol withdrawal. On admission the apo A-II concentration was increased by 48% (P < 0.01) and it was normalized (P < 0.001) during abstention. Among apo A-I containing lipoproteins the most prominent change occurred in Lp A-I:A-II, which fell by 32% (P < 0.01) during 1 week's alcohol withdrawal. During abstention the lipoprotein (a) concentration increased in 10 out of 11 women. In patients cholesteryl ester transfer (CETP) activity increased by 35% (P < 0.01) during 1 week of ethanol withdrawal. On admission postheparin plasma lipoprotein (LPL) and hepatic lipase activities were increased by 25% (P = NS); during 1 week's abstention they both returned to the control level (P < 0.05- < 0.01). In conclusion, chronic alcoholic women display multiple changes of lipoprotein metabolism which are rapidly reversed during abstinence. In contrast to alcoholic men, studied previously by us using the same study design and methods, there was no significant elevation of HDL3 cholesterol and apo A-I. The data suggest that alcohol interferes with several regulatory steps of HDL metabolism which are partly gender dependent.

Adult↗

PubMed1993

Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia.

The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = -0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C-II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C-II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF.

Apolipoprotein C-II↗

PubMed1993

Different acute and chronic effects of acipimox treatment on glucose and lipid metabolism in patients with type 2 diabetes.

To study whether therapeutic reduction of non-esterified fatty acids (NEFA) can be used to improve glucose metabolism, we administered the antilipolytic agent, acipimox, 250 mg four times daily for 4 weeks in eight obese Type 2 diabetic patients. Glucose and NEFA metabolism were assessed before and after treatment with a two-step euglycaemic hyperinsulinaemic clamp (0.25 and 1 mU kg-1 min-1 insulin) combined with infusions of [3-3H] glucose and [1-14C] palmitate. Three days of acipimox treatment reduced 24-h serum NEFA levels by 10%, but the difference disappeared after 4 weeks of treatment mainly due to a two-fold rise in morning NEFA concentrations (p < 0.01). After 3 days of acipimox treatment, fasting and 24-h plasma glucose and serum triglyceride concentrations were significantly reduced (p < 0.05), but no longer after 4 weeks of treatment. Despite the rebound rise in NEFA, acute administration of acipimox still inhibited both oxidative and non-oxidative NEFA metabolism in the basal state (p < 0.01-0.001) and during insulin infusion (p < 0.05-0.001). Inhibition of NEFA metabolism was associated with increased insulin-stimulated glucose uptake (from 3.56 +/- 0.28 to 5.14 +/- 0.67 mumol kg-1 min-1, p < 0.05), mainly due to stimulation of non-oxidative glucose disposal (from 1.74 +/- 0.23 to 3.03 +/- 0.53 mumol kg-1 min-1, p < 0.05). In conclusion, acipimox administered acutely inhibits NEFA appearance (lipolysis), which is associated with improved glucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1993

Gemfibrozil reduces postprandial lipemia in non-insulin-dependent diabetes mellitus.

The effect of gemfibrozil on postprandial lipoprotein metabolism was investigated in a 12-week, randomized, double-blind, placebo-controlled trial in 20 non-insulin-dependent diabetic patients with moderate hypertriglyceridemia. The patients were given a meal containing 78 g of fat and 345,000 units of vitamin A to label chylomicrons and their remnants. Plasma obtained at various times during the fat-load test was separated into six fractions by gradient-density ultracentrifugation. Gemfibrozil reduced the postprandial triglyceride response, measured as the area under the time-dependent concentration curve, on average by 32% in whole plasma, by 38% in the Svedberg flotation unit (Sf) 1,100-3,200 chylomicron fraction, by 36% in Sf 400-1,100 chylomicrons, and by 38% in the Sf 60-400 lipoproteins. Retinyl palmitate, a measure of intestinally derived particles, was reduced in plasma by 34%, in Sf 1,100-3,200 by 46%, in Sf 400-1,100 by 44%, and in Sf 60-400 by 37%. All these reductions were significant in comparison with the placebo group. Particles with Sf < 60 were not significantly affected. In contrast to earlier observations in healthy subjects, no significant negative correlations existed between postprandial lipemia and high density lipoprotein cholesterol or the postheparin lipoprotein lipase activity. The reduction of the potentially atherogenic chylomicron remnants may decrease the risk of atherosclerosis in non-insulin-dependent diabetes mellitus, a hypothesis that awaits testing in prospective studies.

Arteriosclerosis↗

PubMed1993

Thyroid replacement therapy and its influence on postheparin plasma lipases and apolipoprotein-B metabolism in hypothyroidism.

T4 replacement at 150 micrograms/day in a group of six hypothyroid subjects led to the development of a euthyroid state and produced a fall in the cholesterol content of plasma and low and high density lipoproteins (LDL and HDL). The effect of T4 on apolipoprotein-B (apoB) metabolism was followed using radioiodinated very low density lipoprotein1 (VLDL1; 60-400 Svedberg units) and VLDL2 (20-60 Svedberg units). The pretreatment plasma concentration of VLDL1 apoB and its rates of synthesis and catabolism were similar to those in normal subjects. VLDL2 apoB was synthesized at a supranormal rate in hypothyroid subjects, and this led to a doubling of its circulating mass. Treatment did not significantly alter the kinetics of apoB in either VLDL1 or VLDL2. The concentration of intermediate density lipoprotein (IDL) apoB in untreated hypothyroids was 170% of normal and fell during T4 treatment due to stimulation of conversion of LDL (from 0.46 +/- 0.14 to 0.91 +/- 0.30 pools/day; mean +/- SD; P < 0.01). Direct IDL apoB clearance was not altered by treatment, whereas the fractional catabolic rate of LDL increased 76% (from 0.17 +/- 0.06 to 0.27 +/- 0.07 pools/day), leading to a 36% decrement in LDL mass. The stimulation of IDL to LDL conversion during therapy was probably due to a 3-fold increase in hepatic lipase activity (P < 0.02). This change together with the known effects of T4 on LDL receptors largely explained the lipoprotein abnormality in hypothyroidism and the effects of replacement therapy.

Adult↗

PubMed1993

Metabolic consequences of sustained suppression of free fatty acids by acipimox in patients with NIDDM.

To examine whether overnight suppression of free fatty acid levels reduces hepatic glucose production, 20 NIDDM patients were given a slow-release formulation of the antilipolytic agent acipimox, in a double-blind crossover manner at bedtime for 4 wk. During acipimox treatment, serum free fatty acid concentrations were suppressed between 2400 and 0600 by 64% (P < 0.001), but no reduction in hepatic glucose production was observed (2.16 +/- 0.16 vs. 2.23 +/- 0.16 mg.kg-1 x min-1, acipimox vs. placebo). In contrast, from 0800 to 2000 a sustained 50% rise occurred in serum free fatty acids (P < 0.001). As a consequence, the 24-h area under the free fatty acid curve was similar during both treatment periods. In the morning, the rise in free fatty acid concentration occurred despite identical serum acipimox concentrations as those measured at midnight, when free fatty acid levels were suppressed. Although energy expenditure was higher (P < 0.05) during periods of elevated free fatty acid levels, the sums of energy expenditure measured in the morning and in the evening were similar during the acipimox and placebo periods. To exclude that the free fatty acid rise was caused by administration of acipimox only once at bedtime, additional experiments were performed administering acipimox every 2 h for 4 days. Despite similar acipimox concentration on day 1 and day 4 of this frequent dosing regimen, the free fatty acid concentrations were significantly higher on day 4 compared with day 1 (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗

PubMed1993

Regulation of apolipoprotein A-I-containing lipoproteins in IDDM.

In IDDM patients, serum high-density lipoprotein cholesterol concentrations have been reported to be normal or elevated. The spectrum of high-density lipoprotein particles is highly heterogeneous, but no data are available on the subpopulations of high-density lipoprotein in IDDM. We, therefore, studied the spectrum of high-density lipoprotein particles in 86 IDDM patients (51 men and 35 women) 37 +/- 10 yr of age and in 74 sex-, age-, and body mass index-matched healthy nondiabetic subjects. The concentrations of high-density lipoprotein and HDL2 cholesterol were higher in the IDDM group than in the control subjects (P < 0.01). The apoA-I-to-apoA-II ratio was higher in the IDDM patients than in the nondiabetic subjects (P < 0.001) because of an increased concentration of LpA-I particles (61 +/- 17 vs. 53 +/- 15, P < 0.01). LpA-I particles correlated positively with high-density lipoprotein and HDL2 cholesterol in the two groups. Postheparin plasma lipoprotein lipase activity was significantly higher in the IDDM group than in the control group (P < 0.001), whereas postheparin plasma hepatic lipase activities were similar in both groups. Plasma cholesteryl ester transfer protein activity was estimated in an in vitro isotopic assay using exogenous labeled donor (low-density) and acceptor (high-density) lipoproteins in the absence of native lipoproteins. We observed no difference in cholesteryl ester transfer protein activity between the groups, and no significant correlations existed between cholesteryl ester transfer protein activity and high-density lipoprotein subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Does familial hypertriglyceridemia predispose to NIDDM?

OBJECTIVE: To determine the 10-yr incidence of impaired glucose tolerance and NIDDM in families with a clustering of endogenous hypertriglyceridemia. RESEARCH DESIGN AND METHODS: The prospective population study, where the oral glucose tolerance test and the measurement of serum lipids and lipoproteins were performed at the baseline examination and after the 10-yr follow-up, was conducted on 56 subjects (17-60 yr of age at the baseline). The subjects were from six pedigrees with a clustering of endogenous hypertriglyceridemia, and 47 of these subjects attended the follow-up 10 yr later. RESULTS: In the study families, the prevalence of glucose intolerance and NIDDM increased from 15 to 49% (P < 0.001) and from 2 to 21% (P < 0.001), respectively, over the 10-yr period. When grouped according to the baseline serum triglyceride tertiles, 76% (P < 0.01) of the family members with highest serum triglycerides were glucose intolerant (29% impaired glucose tolerance, 47% NIDDM) at follow-up compared with 20% of those with lowest serum triglycerides. In discriminant analysis, including age, body mass index, treatment with thiazides and beta-blocking agents, and 2-h serum insulin concentration, the baseline serum triglycerides still remained as an independent predictor of development of impaired glucose tolerance and NIDDM. CONCLUSIONS: Families with a clustering of hypertriglyceridemia are at increased risk of NIDDM, and in these families elevation of serum triglycerides serves as a risk marker of glucose intolerance and NIDDM.

Adult↗

PubMed1993

Effects of gemfibrozil on low-density lipoprotein particle size, density distribution, and composition in patients with type II diabetes.

OBJECTIVE: To study the effects of gemfibrozil treatment on LDL particle size, density distribution, and composition in NIDDM patients. RESEARCH DESIGN AND METHODS: We performed LDL analyses on 16 NIDDM patients with stable glycemic control. They were randomly allocated to receive either gemfibrozil (n = 8) or a placebo (n = 8) for 3 mo in a double-blind study. The LDL particle size distribution and the particle diameter of the major LDL peak were measured with nondenaturing polyacrylamide gradient gel electrophoresis. The density distribution and composition of LDL were determined with the density gradient ultracentrifugation method. RESULTS: In the gemfibrozil group the mean serum TG concentration decreased by 38%, HDL cholesterol concentration increased by 10%, and LDL cholesterol concentration by 17% (P < 0.05). During gemfibrozil therapy the mean particle diameter of the major LDL peak increased from 244 to 251 A (P < 0.05), whereas in the placebo group the mean LDL particle diameter remained unchanged. We found an inverse correlation between the changes of serum TG and the particle diameters of the major LDL peak (r = 0.85, P < 0.01). Gemfibrozil produced a shift in the LDL density distribution toward lower density. The mean peak density decreased from 1.0371 to 1.0345 g/ml because of a significant rise in the light LDL concentration from 141.0 to 183.2 mg/dl (P < 0.05), whereas the concentration of dense LDL had a tendency to decrease. In the placebo group the LDL density distribution did not change. Gemfibrozil increased the CE-to-TG ratio in LDL core lipids by 27% (P < 0.05); otherwise, the LDL composition was only slightly affected. CONCLUSIONS: The results indicate gemfibrozil-induced changes in LDL properties in NIDDM patients are similar to those previously reported in nondiabetic individuals and are related to changes in serum TG level.

Apolipoproteins B↗

PubMed1993

Prevalence of familial hypercholesterolemia among young north Karelian patients with coronary heart disease: a study based on diagnosis by polymerase chain reaction.

Two deletions of the low density lipoprotein (LDL) receptor gene account for about 90% of the mutations that cause familial hypercholesterolemia (FH) in eastern Finland. The FH-Helsinki mutation deletes exons 16, 17 and a portion of exon 18, while the FH-North Karelia allele is characterized by a deletion of seven nucleotides from exon 6 of the LDL receptor gene. We developed a DNA assay based on the use of polymerase chain reaction (PCR) which simultaneously detects both of these mutations. We have screened 90 young (< 45 years) eastern Finns with symptomatic coronary heart disease (CHD) for the presence of these FH genes. One or the other of the mutations was present in 4 out of 55 survivors of acute myocardial infarction (AMI) and 4 out of 35 patients with angina pectoris (AP), but in none of 50 healthy controls of similar age. These data show a relatively high prevalence of confirmed FH in young CHD patients (AMI and MI combined: 8/90, or 9%), and also demonstrate the feasibility of PCR techniques in diagnosis of FH among populations with enrichment of specific types of LDL receptor gene mutations.

Adult↗

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↗