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  • 1
    Electronic Resource
    Electronic Resource
    Study of porcine and human isophane (NPH) insulins in normal subjects (1984)
    Springer
    Diabetologia 26 (1984), S. 261-265 
    Details
    ISSN: 1432-0428
    Keywords: Porcine NPH insulin ; semi-synthetic and biosynthetic human NPH insulin ; pharmacokinetics ; pharmacodynamics ; normal subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, ‘semi-synthetic’ and ‘biosynthetic’ human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3–5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the ‘intermediate-acting’ NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00283647
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  • 2
    Electronic Resource
    Electronic Resource
    Application of decision theory in understanding food choice behavior of hatchling loggerhead sea turtles and chemosensory imprinting in juvenile loggerhead sea turtles (1989)
    Springer
    Cellular and molecular life sciences 45 (1989), S. 202-205 
    Details
    ISSN: 1420-9071
    Keywords: Feeding behavior ; food choice ; sea turtles ; decision making ; imprinting ; chemoreception
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Food choice behavior of hatchling loggerhead sea turles,Caretta caretta, and chemosensory choice behavior of junvenile loggerhead sea turtles artificially imprinted prior to emergence from the nest were examined using models derived from choice threshold and set releasing value theories of decision making. Modelling results indicate that food choice behavior of hatchlings is better described by a model based on set releasing value theory and that choice behavior of chemically imprinted juveniles is better described by a model based on choice threshold theory.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01954878
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  • 3
    Electronic Resource
    Electronic Resource
    Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models (1991)
    Springer
    Diabetologia 34 (1991), S. 139-143 
    Details
    ISSN: 1432-0428
    Keywords: Rabbits ; diabetes ; hypercholesterolaemia ; lipoproteins ; cholesterol metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7α-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models — the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL2 cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7α-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group, HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418266
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  • 4
    Electronic Resource
    Electronic Resource
    Cellular cholesterol regulation — A defect in the Type 2 (non-insulin-dependent) diabetic patient in poor metabolic control (1990)
    Springer
    Diabetologia 33 (1990), S. 93-99 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; LDL ; cholesterol ; esterification ; glycosylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p 〈 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401046
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  • 5
    Electronic Resource
    Electronic Resource
    Alterations in apolipoprotein B-48 in the postprandial state in NIDDM (1994)
    Springer
    Diabetologia 37 (1994), S. 1259-1264 
    Details
    ISSN: 1432-0428
    Keywords: Key words Apolipoprotein B-48 ; triglyceride-rich lipoproteins ; NIDDM ; cholesterol ; triglyceride.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The intestine is a major site of cholesterol synthesis and produces apolipoprotein B-48, which is critical for intestinal cholesterol absorption and secretion. The purpose of this study was to examine postprandial changes in apolipoprotein B-48 in diabetes. Six non-insulin-dependent diabetic patients and six non-diabetic control subjects were given a high-fat meal (1300 kcal) and blood samples were taken pre- and postprandially, from which the triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (density 〈 1.006 g/ml). Apolipoprotein B-48 was separated on 4–15 % gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Total protein, triglyceride and cholesterol in the triglyceride-rich lipoprotein fraction, blood glucose, and serum insulin were also measured. Diabetic patients exhibited a postprandial triglyceride-rich apolipoprotein B-48 profile significantly different from that of control subjects (p 〈 0.05). The triglyceride and total protein concentration in the triglyceride-rich lipoprotein fraction mirrored the post-prandial profile and apolipoprotein B-48 in both groups. Significantly different patterns for triglyceride (p 〈 0.02) and total protein (p 〈 0.05) following the fat-rich meal were observed in the two groups. Fasting and postprandial triglyceride-rich lipoprotein cholesterol and total apolipoprotein B were significantly higher in diabetic patients than in control subjects (p 〈 0.05). Since apolipoprotein B-48 is the structural protein of intestinally-derived lipoprotein particles, these studies suggest an abnormality in intestinal lipoprotein metabolism in diabetes. [Diabetologia (1994) 37: 1259–1264]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00399800
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  • 6
    Electronic Resource
    Electronic Resource
    Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition, oxidisability and function of low and high density lipoproteins (1996)
    Springer
    Diabetologia 39 (1996), S. 667-676 
    Details
    ISSN: 1432-0428
    Keywords: Non-insulin-dependent diabetes mellitus ; low density lipoprotein oxidation ; low density lipoprotein fatty acids ; lipid peroxidation ; conjugated dienes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p〈0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p〈0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p〈0.05) before diet and it increased significantly after diet (p〈0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r=0.46, p〈0.05 and r=0.49, p〈0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476±30 to 390±20 nmol/mg protein p〈0.05 and for control subjects from 350±36 to 198±30 nmol/mg protein p〈0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4±7.5 to 53.2±6.7 nmol/mg protein for diabetic patients and 45.8±6.4 to 31.6±4.8 nmol/mg protein p〈0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r=0.61, p〈0.05) and control subjects (r=0.91, p〈0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r=0.71, p〈0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00418538
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  • 7
    Electronic Resource
    Electronic Resource
    Two microsatellite repeat polymorphisms flanking opposite ends of the human glucokinase gene: use in haplotype analysis of Welsh Caucasians with Type 2 (non-insulin-dependent) diabetes mellitus (1993)
    Springer
    Diabetologia 36 (1993), S. 409-413 
    Details
    ISSN: 1432-0428
    Keywords: Glucokinase gene ; microsatellite ; polymorphism ; linkage disequilibrium ; haplotypes ; Type 2 (non-insulin-dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The purpose of this study was to evaluate the role of potential glucokinase defects contributing to susceptibility to Type 2 (non-insulin-dependent) diabetes mellitus in Welsh Caucasians. For this analysis, two microsatellite repeat polymorphisms flanking opposite ends of the gene were employed. For a recently described microsatellite (GCK2), located 6 kilobases upstream of islet exon 1, six different sized alleles were observed, with heterozygosity of 0.50 and polymorphism information content 0.44. Combined heterozygosity with another microsatellite repeat (GCK1) was 0.72. Significant linkage disequilibrium was noted between GCK2 and GCK1, suggesting that haplotypes may be a better predictor of Type 2 diabetes than analysis with either microsatellite alone. Using these two markers, the association with Type 2 diabetes was examined. The frequencies of alleles and genotypes at GCK1 did not differ between the patients with Type 2 diabetes (n=157) and control subjects (n=73). Similarly no differences were observed in GCK2 alleles or genotypes. The frequencies of haplotypes, derived from the two markers, also did not differ between the two groups. To investigate the possibility of minor metabolic effects of glucokinase defects, we also studied the association between the GCK alleles or haplotypes and the response profiles to meal tolerance tests. No association was observed between plasma glucose or insulin responses to meal tolerance tests with GCK haplotypes or alleles. These results suggest that glucokinase mutations in Welsh Caucasians are not major determinants of susceptibility to the common type of Type 2 diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00402276
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  • 8
    Electronic Resource
    Electronic Resource
    Oxidation of low-density lipoprotein in NIDDM: its relationship to fatty acid composition (1995)
    Springer
    Diabetologia 38 (1995), S. 1300-1306 
    Details
    ISSN: 1432-0428
    Keywords: Key words Non-insulin-dependent diabetes mellitus ; low-density lipoprotein oxidation ; dietary fatty acids ; low-density lipoprotein composition ; glycated low-density lipoprotein.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The increased risk of atherosclerotic disease in diabetic subjects may be due to enhanced foam cell formation following an increased susceptibility of low density lipoprotein to oxidative modification. This study has compared fatty acid content and lipoprotein oxidisability in 10 non-insulin-dependent diabetic subjects with that in 10 control subjects. Both groups were normocholesterolaemic and the diabetic subjects had higher triglyceride levels (2.2 ± 0.4 vs 1.2 ± 0.2 mmol/l, p 〈 0.05). The fatty acid composition was compared in low density lipoprotein following Folch extraction, separation by thin layer chromatography (for the lipid classes) and analysis by gas liquid chromatography. Low density lipoprotein oxidisability was assessed by conjugated diene and thiobarbituric acid reacting substance formation in the presence of copper ions. The esterified/free cholesterol ratio was higher in the low density lipoprotein from patients compared to control subjects (2.9 ± 0.1 vs 1.9 ± 0.3, p 〈 0.05). Linoleic acid in the cholesteryl ester fraction of the lipoprotein was higher in the patients than in the control subjects (48.2 ± 2.2 % vs 42.4 ± 3.4 %, p 〈 0.05) as was the total quantity of linoleic acid in the cholesteryl ester fraction (317.8 ± 68.0 vs 213.2 ± 28.0 μg/mg protein, p 〈 0.05) and in the low-density lipoprotein as a whole (443.2 ± 70.0 vs 340.2 ± 28.2 μg/mg protein, p 〈 0.05). Lipoprotein oxidisability was also increased in the diabetic group with increased formation of thiobarbituric acid reacting substances (35.6 ± 7.2 vs 22.3 ± 3.5 nmol/mg protein, p 〈 0.05, increased total diene formation (502 ± 60 vs 400 ± 30 nmol/mg protein, p 〈 0.05) and increased rate of diene formation (7.2 ± 0.6 vs 5.1 ± 0.9 nmol diene · mg protein–1· min–1, p 〈 0.05). This study indicates that low-density lipoprotein from diabetic subjects is more susceptible to oxidation. This could, in vivo, accelerate foam-cell formation thereby increasing atherosclerotic risk in diabetic subjects. [Diabetologia (1995) 38: 1300–1306]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401762
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  • 9
    Electronic Resource
    Electronic Resource
    Impact of initial treatment on renal function in newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus (1993)
    Springer
    Diabetologia 36 (1993), S. 734-740 
    Details
    ISSN: 1432-0428
    Keywords: Type 2 (non-insulin-dependent) diabetes mellitus ; renal haemodynamics ; improved glycaemic control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p〈0.01); fasting plasma glucose (p〈0.001); glycated haemoglobin (HbA1) (p〈0.001); systolic blood pressure (p〈0.01); and diastolic blood pressure (p〈0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min−1 (p〈0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min−1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) μg·min−1 (p〈0.01). Changes in glomerular filtration rate (Δ values) were inversely correlated with presentation values (p〈0.001), and positive relationships were observed with Δ effective renal plasma flow (p〈0.01), and Δ glycated haemoglobin (p〈0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min−1 demonstrated significant reduction in glomerular filtration rate (n=31; p〈0.001), whilst those with original values less than 120 ml·min−1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p〈0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p〈0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min−1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401144
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  • 10
    Electronic Resource
    Electronic Resource
    Lipoprotein composition in NIDDM: effects of dietary oleic acid on the composition, oxidisability and function of low and high density lipoproteins (1996)
    Springer
    Diabetologia 39 (1996), S. 667-676 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Non-insulin-dependent diabetes mellitus ; low density lipoprotein oxidation ; low density lipoprotein fatty acids ; lipid peroxidation ; conjugated dienes.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Oxidation of low density lipoprotein (LDL) plays an important role in the pathogenesis of atherosclerosis and is related to the fatty acid composition which is altered in diabetes mellitus. This study examines the relationship between the fatty acid composition of LDL and high density lipoprotein (HDL) and lipoprotein oxidation. A group of nine non-insulin-dependent diabetic (NIDDM) patients were compared to seven healthy control subjects before and after a high monounsaturated diet. Lipoproteins were isolated and oxidisability was measured by conjugated diene formation and lipid peroxide analysis. Serum HDL cholesterol was significantly lower in the diabetic patients. LDL cholesteryl ester linoleic acid in the diabetic patients was significantly higher at baseline and decreased after diet (p 〈 0.05) while oleic acid increased in both diabetic and non-diabetic subjects (p 〈 0.05). HDL cholesteryl ester oleic acid was lower in the diabetic patients compared with control subjects (p 〈 0.05) before diet and it increased significantly after diet (p 〈 0.05). LDL lipid peroxides and conjugated diene formation were related to LDL glycation (r = 0.46, p 〈 0.05 and r = 0.49, p 〈 0.05, respectively). Both decreased following diet (lipid peroxides for diabetic patients from 476 ± 30 to 390 ± 20 nmol/mg protein p 〈 0.05 and for control subjects from 350 ± 36 to 198 ± 30 nmol/mg protein p 〈 0.05). HDL conjugated diene formation decreased in both groups after diet but only significantly in the control group (55.4 ± 7.5 to 53.2 ± 6.7 nmol/mg protein for diabetic patients and 45.8 ± 6.4 to 31.6 ± 4.8 nmol/mg protein p 〈 0.05 for control subjects). There was a positive correlation between LDL lipid peroxide formation and percentage of cholesteryl ester linoleic acid in LDL from diabetic patients (r = 0.61, p 〈 0.05) and control subjects (r = 0.91, p 〈 0.01). Fatty acid composition of LDL was reflected in the composition of HDL. In the presence of HDL lipoprotein peroxidation decreased. This decrease in lipoprotein peroxidation was positively related to the percentage of linoleic acid in LDL (r = 0.71, p 〈 0.05). This study confirms the close relationship between the fatty acid composition of LDL and HDL and demonstrates the importance of the fatty acid composition of the cholesteryl ester fraction in relation to LDL oxidation in diabetes. Linoleic acid in HDL appears to be a protecting factor against oxidation. [Diabetologia (1996) 39: 667–676]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050494
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