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Your search keyword '"Raalte, D.H. van"' showing total 4 results
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4 results on '"Raalte, D.H. van"'

1. Peroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria

Author

Garsen, M., Buijsers, B., Sol, M., Gockeln, L., Sonneveld, R., Kuppevelt, T.H. van, Graaf, M.J.J. de, Born, J. van den, Kamps, J.A.A.M., Raalte, D.H. van, Meer, R.W. van der, Lamb, H.J., Hillebrands, J.L., Rabelink, T.J., Maciej Hulme, M.L., Krenning, G., Nijenhuis, T., Vlag, J. van der, Garsen, M., Buijsers, B., Sol, M., Gockeln, L., Sonneveld, R., Kuppevelt, T.H. van, Graaf, M.J.J. de, Born, J. van den, Kamps, J.A.A.M., Raalte, D.H. van, Meer, R.W. van der, Lamb, H.J., Hillebrands, J.L., Rabelink, T.J., Maciej Hulme, M.L., Krenning, G., Nijenhuis, T., and Vlag, J. van der

Abstract

Item does not contain fulltext

Published
2023

2. Glucocorticoid receptor gene polymorphisms are associated with reduced first-phase glucose-stimulated insulin secretion and disposition index in women, but not in men

Author

Raalte, D.H. van, Leeuwen, N. van, Simonis-Bik, A.M., Nijpels, G., Haeften, T.W. van, Schafer, S.A., Boomsma, D.I., Kramer, M.H.H., Heine, R.J., Maassen, J.A., Staiger, H., Machicao, F., Haring, H.U., Slagboom, P.E., Willemsen, G., Geus, E.J. de, Dekker, J.M., Fritsche, A., Eekhoff, E.M., Diamant, M., Hart, L.M. 't, Internal medicine, General practice, Epidemiology and Data Science, ICaR - Circulation and metabolism, EMGO - Lifestyle, overweight and diabetes, Biological Psychology, and EMGO+ - Lifestyle, Overweight and Diabetes

Subjects
Netherlands Twin Register (NTR), Male, Genotype, Polymorphism, Single Nucleotide, ss-cell function, Cross-Sectional Studies, Receptors, Glucocorticoid, Sex Factors, SDG 3 - Good Health and Well-being, Haplotypes, Hyperglycemia, Insulin-Secreting Cells, Glucose Intolerance, Insulin Secretion, glucocorticoid receptor, Humans, Insulin, Female, Insulin Resistance, polymorphisms
Abstract

Glucocorticoids are efficacious anti-inflammatory agents, but, in susceptible individuals, these drugs may induce glucose intolerance and diabetes by affecting β-cell function and insulin sensitivity. We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of β-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance.A cross-sectional cohort study was conducted in four academic medical centres in the Netherlands and Germany. Four hundred and forty-nine volunteers (188 men; 261 women) were recruited with normal glucose tolerance (n=261) and impaired glucose tolerance (n=188). From 2-h hyperglycaemic clamps, first- and second-phase glucose-stimulated insulin secretion, as well as insulin sensitivity index and disposition index, were calculated. All participants were genotyped for the functional NR3C1 polymorphisms N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/6190), 9β A/G (rs6198) and ThtIIII (rs10052957). Associations between these polymorphisms and β-cell function parameters were assessed.In women, but not in men, the N363S polymorphism was associated with reduced disposition index (P=1.06 10(-4) ). Also only in women, the ER22/23EK polymorphism was associated with reduced first-phase glucose-stimulated insulin secretion (P=0.011) and disposition index (P=0.003). The other single-nucleotide polymorphisms were not associated with β-cell function. Finally, none of the polymorphisms was related to insulin sensitivity.The N363S and ER22/23EK polymorphisms of the NR3C1 gene are negatively associated with parameters of β-cell function in women, but not in men.

Published
2012
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3. Prednisolone-induced beta cell dysfunction is associated with impaired endoplasmic reticulum homeostasis in INS-1E cells.

Author

Linssen, M.M., Raalte, D.H. van, Toonen, E.J.M., Alkema, W., Zon, G.C. van der, Dokter, W.H., Diamant, M., Guigas, B., Ouwens, D.M., Linssen, M.M., Raalte, D.H. van, Toonen, E.J.M., Alkema, W., Zon, G.C. van der, Dokter, W.H., Diamant, M., Guigas, B., and Ouwens, D.M.

Abstract

1 november 2011, Item does not contain fulltext, Glucocorticoids (GCs), such as prednisolone (PRED), are widely prescribed anti-inflammatory drugs, but their use may induce glucose intolerance and diabetes. GC-induced beta cell dysfunction contributes to these diabetogenic effects through mechanisms that remain to be elucidated. In this study, we hypothesized that activation of the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress could be one of the underlying mechanisms involved in GC-induced beta cell dysfunction. We report here that PRED did not affect basal insulin release but time-dependently inhibited glucose-stimulated insulin secretion in INS-1E cells. PRED treatment also decreased both PDX1 and insulin expression, leading to a marked reduction in cellular insulin content. These PRED-induced detrimental effects were found to be prevented by prior treatment with the glucocorticoid receptor (GR) antagonist RU486 and associated with activation of two of the three branches of the UPR. Indeed, PRED induced a GR-mediated activation of both ATF6 and IRE1/XBP1 pathways but was found to reduce the phosphorylation of PERK and its downstream substrate eIF2alpha. These modulations of ER stress pathways were accompanied by upregulation of calpain 10 and increased cleaved caspase 3, indicating that long term exposure to PRED ultimately promotes apoptosis. Taken together, our data suggest that the inhibition of insulin biosynthesis by PRED in the insulin-secreting INS-1E cells results, at least in part, from a GR-mediated impairment in ER homeostasis which may lead to apoptotic cell death.

Published
2011

4. GLP-1 receptor agonism to improve cardiometabolic health

Author

Eyk, H.J. van, Rensen, P.C.N., Lamb, H.J., Jazet, I.M., Pijl, H., Rossem, E.F.C. van, Raalte, D.H. van, Geehoed-Duijvesteijn, P.H., and Leiden University

Subjects
South Asian, Type 2 diabetes, Energy expenditure, Obesity, Brown adipose tissue, Ectopic fat, Cardiovascular function, Glucagon-like peptide-1 (GLP-1)
Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively new treatment option for obesity and type 2 diabetes. Treatment has been shown to result in in weight loss and improved glycemic control. In this thesis, the effects of treatment on the different adipose tissue depots and on cardiac function are described. In a randomised controlled trial, we treated patients with type 2 diabetes from South Asian descent, a population with increased risk to develop type 2 diabetes and cardiovascular disease compared to Western Europeans, with liraglutide, a GLP-1 receptor agonist, or placebo, and studied these subjects with MRI. We concluded that liraglutide and possibly other GLP-1 receptor agonists can be a good strategy to reduce the volume of visceral adipose tissue. This reduction was accompanied by a significant improvement of glycemic control. Lastly, we provided evidence that liraglutide does not improve cardiac function and myocardial tissue characteristics and thus does not improve diabetic cardiomyopathy. In addition, in another study, we studied the mechanism behind GLP-1 receptor agonism induced weight loss and concluded that liraglutide induces weight loss in humans by decreasing energy intake rather than by activating brown adipose tissue or increasing energy expenditure.

Published
2023

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