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VRIjE UNIVERSITEIT Diabetogenic Effects of Glucocorticoid Drugs: The Knowns and The Unknowns ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad Doctor aan de Vrije Universiteit Amsterdam, op gezag van de rector magnificus prof.dr. L.M. Bouter, in het openbaar te verdedigen ten overstaan van de promotiecommissie van de Faculteit der Geneeskunde op vrijdag 23 november 2012 om 13.45 uur in de aula van de universiteit, De Boelelaan 1105 door Daniël Henri van Raalte geboren te Amsterdam
Page 2: Diabetogenic Effects of Glucocortic
Page 8: Promotor: prof.dr. M. Diamant
Page 12: CoNTENT Part I Introduction Chapter
Page 18: PART Introduction I
Page 24: Chapter 1 General Introduction The
Page 28: Chapter 1 General Introduction and
Page 32: Chapter 1 General Introduction The
Page 36: Chapter 1 General Introduction REFE
Page 40: Chapter 1 General Introduction 32.
Page 48: Chapter 2 Glucocorticoids: metaboli
Page 52: Chapter 2 Glucocorticoids: metaboli
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Chapter 2 Glucocorticoids: metaboli
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Chapter 3 Prednisolone-Induced Beta
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INTRoDUCTIoN Glucocorticoids (GCs),
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content was measured in acid-ethano
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Figure 2. Effects of prednisolone o
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Figure 5. Effects of prednisolone a
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Prednisolone increases expression o
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activity of protein phosphatase(s)
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REFERENCES 1. Clore jN, Thurby-Hay
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29. Shimizu N, Yoshikawa N, Ito N,
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Chapter 4 Acute and 2-Week Exposure
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Glucocorticoids (GCs), such as pred
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meal beginning immediately after th
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Table 1 (Acute study). Subject char
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Figure 3. A two-week treatment with
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prednisolone, as the most widely pr
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REFERENCES 1. Schacke H, Docke WD,
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Chapter 5 Islet-cell Dysfunction In
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Glucocorticoids (GCs) are the corne
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Hyperinsulinemic-euglycemic clamp a
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called the potentiation factor rati
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iAUC: β=0.126; P=0.638; R 2 =0.119
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Figure 3. Postprandial responses at
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Safety and tolerability: One subjec
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towards withdrawal of vagal activit
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29. Hamamdzic D, Duzic E, Sherlock
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Supplementary Figure 3. Patient flo
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Chapter 6 Glucocorticoid Receptor G
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Excess glucocorticoid (GC) levels i
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Figure 1. Schematic overview of the
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N363S (rs6195) AA 222 766 (722-812)
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possibility to have missed subtle e
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14. Russcher H, Smit P, van den Akk
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SUPPLEMENTAL FILES Supplementary Fi
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Supplemental Table 2. Major inclusi
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Haplotype 5 0 223 767 (724-813) 248
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Chapter 7 GLP-1 prevents glucocorti
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PART Mechanisms of glucocorticoid-i
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Chapter 8 Glucocorticoids affect in
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Chapter 9 Glycosphingolipid Metabol
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INTRoDUCTIoN Glucocorticoids (GCs)
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Experimental protocol: The design o
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oxidative phosphorylation (OXPHOS)
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Table 3. Mitochondrial respiration
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prednisolone 30 mg group, and the c
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29. Kabayama K, Sato T, Saito K, Lo
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Chapter 10 Glucocorticoid Treatment
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Glucocorticoids (GCs) represent the
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capillary recruitment. Capillary re
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elatively small numbers in each gro
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Table 2. Metabolic parameters and b
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Table 3. Capillary density before a
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Prednisolone and insulin signaling
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DISCUSSIoN This is the first study
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glucose uptake suggesting that the
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15. de jongh RT, Serne EH, RG Ij, d
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SUPPLEMENTARy MATERIAL Supplemental
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Chapter 11 Glucocorticoids alter Su
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Glucocorticoids (GCs) are important
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Adipose tissue was washed with ster
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Figure 1. Effects of glucocorticoid
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Impaired insulin action in adipose
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REFERENCES 1. van Raalte DH, Ouwens
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30. Ouchi N, Parker JL, Lugus JJ, W
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Chapter 12 Angptl4 in glucocorticoi
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PART Metabolic Effects of Glucocort
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Chapter 13 Glucocorticoids in acute
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Chapter 14 Glucose Tolerance, Insul
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INTRoDUCTIoN Rheumatoid arthritis (
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independent ethics committee approv
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Glucose tolerance state: The preval
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Data represent means ± standard de
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**** Number of DMARDs (both synthet
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Effect modification: As compared to
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described here, may even be underes
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15. Wolfe F, Michaud K. Corticoster
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PART Discussion V
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Chapter 15 General Discussion Gluco
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Chapter 15 General Discussion Studi
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Chapter 15 General Discussion Figur
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Chapter 15 General Discussion AMP-a
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Chapter 15 General Discussion shown
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Chapter 15 General Discussion decre
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Chapter 15 General Discussion Inter
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Chapter 15 General Discussion Mecha
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Chapter 15 General Discussion and a
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Chapter 15 General Discussion and p
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Chapter 15 General Discussion short
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Chapter 15 General Discussion Table
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Chapter 15 General Discussion REFER
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Chapter 15 General Discussion 30. S
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Chapter 15 General Discussion 58. L
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Chapter 15 General Discussion 88. F
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Chapter 15 General Discussion 119.
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Nederlandse Samenvatting Diabetogen
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het bleek ook heel effectief bij de
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door prednisolon behandeling. In di
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In deel 4 van mijn proefschrift bes
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Dankwoord Acknowledgements
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Geachte Dr. Ouwens, beste Margriet.
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Dr. Kersten, beste Sander, veel dan
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Biography
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Daniël Henri van Raalte was born o
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List of Publications 1. van Genugte
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List of Publications 20. van Raalte
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List of co-author affiliations Andr
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List of co-author affiliations Jos
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List of co-author affiliations Timo
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Color Figures Chapter 1 Figure 1. O
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