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  • 1
    Electronic Resource
    Electronic Resource
    Very low density lipoprotein subfraction abnormalities in IDDM patients: any effect of blood glucose control? (1995)
    Springer
    Diabetologia 38 (1995), S. 1419-1424 
    Details
    ISSN: 1432-0428
    Keywords: Lipoproteins ; VLDL subfractions ; insulin-dependent diabetes mellitus ; blood glucose control ; lipid concentration ; lipolytic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c〉8%, n=18) or good blood glucose control (group 2, HbA1c〈8%, n=16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175–400; intermediate, Sf 100–175; small, Sf 20–100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49±2%; p〈0.005; group 2: 51±3%, p〈0.01; control subjects 40±2%) (mean ± SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35±4 vs 27±3 mg/dl, p=0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254±19 mU/ ml, p〈0.05; group 2: 202±19 mU/ml, p〈0.005; control subjects 317±31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400602
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  • 2
    Electronic Resource
    Electronic Resource
    Increased activity of the insulin-like growth factor system in mesangial cells cultured in high glucose conditions. Relation to glucose-enhanced extracellular matrix production (1996)
    Springer
    Diabetologia 39 (1996), S. 775-784 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Insulin-like growth factor-I ; II ; binding proteins ; receptors ; transforming growth factor-b ; extracellular matrix ; mesangial cell ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent evidence suggests that several growth factors participate in diabetic glomerular disease by mediating increased extracellular matrix accumulation and altered cell growth and turnover leading to mesangial expansion. Transforming growth factor (TGF)-β has been demonstrated to be upregulated both in vivo and in vitro, whereas studies on the activity of the renal insulin-like growth factor (IGF) system in experimental diabetes have provided conflicting results. We investigated the effects of prolonged exposure (4 weeks) of cultured human and rat mesangial cells to high (30 mmol/l) glucose vs iso-osmolar mannitol or normal (5.5 mmol/l) glucose levels on: 1) the autocrine/paracrine activity of the IGF system (as assessed by measuring IGF-I and II, IGF-I and II receptors, and IGF binding proteins); and, in parallel, on 2) TGF-β1 gene expression; 3) matrix production; and 4) cell proliferation. High glucose levels progressively increased the medium content of IGF-I and the mRNA levels for IGF-I and IGF-II, increased IGF-I and IGF-II binding and IGF-I receptor gene expression, and reduced IGF binding protein production. TGF-β1 transcripts and matrix accumulation and gene expression were increased in parallel, whereas cell proliferation was reduced. Iso-osmolar mannitol did not affect any of the above parameters. These experiments demonstrated that high glucose levels induce enhanced mesangial IGF activity, together with enhanced TGF-β1 gene expression, increased matrix production, and reduced cell proliferation. It is possible that IGFs participate in mediating diabetes-induced changes in matrix turnover leading to mesangial expansion, by acting in a paracrine/autocrine fashion within the glomerulus. [Diabetologia (1996) 39: 775–784]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050510
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  • 3
    Electronic Resource
    Electronic Resource
    Regulatory role of eicosanoids in extracellular matrix overproduction induced by long-term exposure to high glucose in cultured rat mesangial cells (1996)
    Springer
    Diabetologia 39 (1996), S. 1055-1062 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Extracellular matrix ; transforming growth factor-β ; prostaglandins ; thromboxane ; mesangial cell ; diabetes mellitus.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Accumulation of extracellular matrix in the mesangium and altered renal eicosanoid synthesis are two prominent features of diabetic glomerular disease. We investigated the relationship between eicosanoid and extracellular matrix production in rat mesangial cells cultured under high glucose vs normal glucose conditions. Long-term exposure of rat mesangial cells to high glucose, but not to iso-osmolar mannitol, significantly increased extracellular matrix accumulation and gene expression and transforming growth factor-β (TGF-β) mRNA levels, and decreased prostaglandin (PG) E2 synthesis without affecting production of either thromboxane (TX) B2 or PGF2 a, with respect to cells incubated in normal glucose. Addition of exogenous PGE2 resulted in a dose-dependent reduction of matrix protein and mRNA levels and TGF-β gene expression in cells cultured in either normal or high glucose conditions, whereas exposure to exogenous PGF2α produced a significant increment in matrix production and matrix and TGF-β gene expression in cells grown in normal glucose, but only a slight increase in those cultured in high glucose. Stimulation of endogenous endoperoxide metabolism towards PGE2 and PGF2α synthesis with FCE-22,178, a drug originally developed as TXA2 synthase inhibitor, resulted in a dose-dependent decrease in matrix accumulation and matrix and TGF-β gene expression which was suppressed by co-incubation with the cyclo-oxygenase inhibitor fenoprofen blocking the FCE-22,178-enhanced PG production. In both cell lines, the rate of synthesis of TXA2 was very low and the selective blockade of its synthesis (by two other TXA2 synthase inhibitors, OKY-046 and Ridogrel) or action (by the TXA2 receptor antagonist BM-13,177) did not alter matrix production or TGF-β mRNA levels. These results suggest that the cyclo-oxygenase pathway is involved in the regulation of matrix changes induced by high glucose in rat mesangial cells; the reduced production of PGE2 may enhance the synthesis or potentiate the effect of stimulators of ECM formation such as TGF-β, whereas TXA2 does not appear to be involved. These data also indicate that glucose-enhanced mesangial matrix accumulation may be prevented by exogenous PGE2 or by drugs capable of increasing endogenous PGE2 synthesis. [Diabetologia (1996) 39: 1055–1062]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400654
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  • 4
    Electronic Resource
    Electronic Resource
    Abnormal distribution of VLDL subfractions in Type 1 (insulin-dependent) diabetic patients: could plasma lipase activities play a role? (1993)
    Springer
    Diabetologia 36 (1993), S. 155-160 
    Details
    ISSN: 1432-0428
    Keywords: Lipoproteins ; VLDL subfractions ; diabetes mellitus ; lipid composition ; lipolytic enzymes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Very low density lipoproteins (VLDL) have an abnormal lipid composition in Type 1 (insulin-dependent) diabetic patients. Since VLDL represent a heterogeneous lipoprotein class, this might be due either to a shift in the distribution or to an abnormal composition of VLDL subclasses or both. In order to investigate these possibilities and to evaluate possible pathogenetic mechanisms, lipid composition (non-esterified and esterified cholesterol, triglycerides, phospholipids) of four VLDL subfractions of decreasing size (A: Svedberg flotation unit [Sf]〉400, B: Sf, 175–400, C: Sf 100–175, D: Sf 20–100), isolated by density gradient preparative ultracentrifugation, and plasma post-heparin lipolytic activity (lipoprotein lipase and hepatic lipase) were evaluated in 13 male normolipidaemic insulin-dependent diabetic patients in good glycaemic control (HbA1c 6.9±0.5%) (mean±SEM) and 9 male control subjects matched for age, body mass index and plasma lipid values. Compared to control subjects, diabetic patients showed a reduced total lipid concentration of VLDL of intermediate size (B and C) reaching statistical significance only for VLDL C (0.16±0.02 vs 0.24±0.03 mmol/l; p 〈0.05). Expressing each VLDL subfraction as percent of the total VLDL lipid concentration, a significant decrease in particles of intermediate size (C) (20.5±1.6 vs 27.9±1.5%; p 〈0.005) was present, which was compensated by an increase in the smallest ones (D) (50.5±2.7 vs 37.4±3.1%; p 〈0.05). VLDL of smaller size were also the only particles with an abnormal composition consisting of a significant increase in esterified cholesterol (12.2±0.8 vs 8.7±1.2%, p 〈0.01). Post-heparin hepatic lipase activity was significantly reduced in diabetic patients as compared to control subjects (232.9±27.9 vs 332±42.3 mU/ml; p 〈0.05) while post-heparin lipoprotein lipase activity was similar in the two groups. Furthermore, hepatic lipase activity was inversely related to the percentage of smaller VLDL (D)(r=−0.72; p 〈0.01) in diabetic patients and this relationship was independent of changes in intermediate VLDL (VLDL C). In conclusion the data suggest that Type 1 diabetic patients, although normolipidaemic and in good blood glucose control, show a shift in the distribution of VLDL subclasses toward VLDL of a smaller size which also have an abnormal composition. The different distribution of VLDL subfractions seems to be related to a reduced hepatic lipase activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400698
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  • 5
    Electronic Resource
    Electronic Resource
    Presence of very low density lipoprotein compositional abnormalities in Type 1 (insulin-dependent) diabetic patients; effects of blood glucose optimisation (1988)
    Springer
    Diabetologia 31 (1988), S. 884-888 
    Details
    ISSN: 1432-0428
    Keywords: Lipoproteins ; Type 1 (insulin-dependent) diabetes ; blood glucose control ; lipoprotein composition ; atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma lipoprotein compositional abnormalities were investigated in eight normolipidaemic (plasma cholesterol 〈5.70 mmol/l; triglyceride 〈2.03 mmol/l) young male Type 1 (insulin-dependent) diabetic patients (before and after a short period of optimised blood glucose control) and in nine healthy control subjects, matched for sex, age and body mass index. Free and esterified cholesterol, triglyceride, phospholipids were assayed in all lipoprotein classes (VLDL, IDL, LDL) and in HDL subclasses (HDL2 and HDL3); apoB was measured only in very low density lipoproteins (VLDL). All VLDL constituents were increased in the diabetic group, the differences being more striking for apoB (6.0±1.1 mg/dl vs 2.0±0.1 mg/dl, p〈0.02), free cholesterol (0.27±0.04 mmol/l vs 0.13±0.02 mmol/l, p〈0.02) and esterified cholesterol (0.32±0.08 mmol/l vs 0.13±0.01 mmol/l, p〈0.05). Also HDL subfractions showed differences between the two groups: all HDL2 constituents were increased, while in HDL3 only triglyceride was significantly increased (0.11±0.01 mmol/l vs 0.08±0.004 mmol/l, p〈0.02). After two weeks of optimised blood glucose control all VLDL constituents were reduced and particularly: esterified cholesterol (−39%, p〈0.02), free cholesterol (−37%, p〈0.05), apoB (− 35%, p〈0.05). Expressing each VLDL constituent as percent of the total lipoprotein mass, it was evident that the diabetic VLDL was rich in cholesterol both esterified (8.4±1.0% vs 5.4±0.5%, p〈0.02) and free (8.5±0.7% vs 5.5±0.3%, p〈0.001), apo B (5.1±0.6% vs 2.6±0.3%, p〈0.001) and depleted in triglyceride (57.0±1.7% vs 64.1±1.7%, p〈0.001). Two weeks of optimised blood glucose control were not able to correct the abnormal composition of VLDL. In conclusion, Type 1 (insulin-dependent) diabetic patients, although normolipidaemic, show an abnormal VLDL composition suggesting an increased prevalence of smaller and, possibly, more atherogenic VLDL particles. This abnormality is not corrected by a short period of blood glucose optimisation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265371
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