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Contribution of glucotoxicity and glucolipotoxicity to the developmentof type 2 diabetes
GlucotoxicityChronic exposure to high glucose in β-cell lines:Insulin mRNAInsulin promoter activityInsulin gene transcription factors(STF-1/PDX-1/IPF-1/IDX-1, MafA, RIPE3b1 activator)Glucose-stimulated insulin secretionInsulin contentChronic exposure to low glucoseAll preserved(RP Robertson et al J Clin Invest 97:1041-1046, 1996)
Page 1 and 2: β cell and Hyperglycemia in Type 2
Page 3: Schema of five stages of progressio
Page 8 and 9: The glucotoxic effect on insulin ge
Page 10 and 11: 1.5†‡Insulin/ b-actin mRNA1.00.
Page 12 and 13: Chronic exposure to high glucose co
Page 15 and 16: γ GCS m RNAGSH level (µmol/mg)444
Page 17 and 18: mesothelial cellsleukocytesGSH leve
Page 19 and 20: γ -GCS Expression : Summary & Conc
Page 21 and 22: Effects of glucose on lipid partiti
Page 23 and 24: (McGarry JD Diabetes 51: 7-18, 2002
Page 25 and 26: Oxidative stressAdaptiveresponseEPO
Page 27 and 28: Control MetforminLeptin (ug) 0 0.1
Page 29 and 30: Lipotoxicity in Human Pancreatic Is
Page 31 and 32: Metformin in β cells• To evaluat
Page 33 and 34: 100Metformin 25 µg/mlFluorescence
Page 35 and 36: Metformin : Summary & Conclusion•
Page 37 and 38: Des-fluoro-sitagliptin (DFS):11-Wee
Page 39 and 40: • Complementary action of antioxi
Page 41 and 42: (A)122 Kd80 Kd(B)51 KdDensity (% Co
Page 43 and 44: Protective effect of Heme Oxygenase
Page 45 and 46: HO-1 mRNAβ-actin mRNAAfter HO-1 ad
Page 47 and 48: Lipotoxicity and Type 2 Diabetes
Page 49 and 50: FFAs in the pathogenesisof type 2 d
Page 51 and 52: Glucotoxicity vs. LipotoxicityGluco
Page 53 and 54: Consequences of treating ZDF rats w
Page 55 and 56:
IntestinalLumenLipaseACAT: Acyl Co-
Page 57 and 58:
High glucose levels increase choles
Page 59 and 60:
FAT/CD36*ㅜㅜ ㅜ* p
Page 61 and 62:
• At only lipotoxic condition (5.
Page 63 and 64:
Summary
Page 65 and 66:
• In human studies of type 2 diab
Page 67:
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