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Metformin↓ ACC activityPhosphorylation/activation of AMPK↓ SREBP-1 expression↓ SREBP-1 activity↓ Hepatic gene expression : FAS,L-PK,S14↑ Muscle glucose transport?↓ Hepatic FA, VLDL synthesis(↑hepatic FA oxidation)↓ Hepatic glucose production↓ Hapatic steatosis↑ Liver insulin sensitivity↓ Plasma glucose, triglyceride, FFAModel for the mechanism by which metformin mediates effects on lipid and glucose metabolism
Control MetforminLeptin (ug) 0 0.1 1 0 0.1 1pAMPKAMPKpSTAT3STAT3pAMPK/AMPK, arbitary units6543210* **0 0.6 15 0 0.6 15pSTAT3/STAT3963** **,††**Leptin (ug/D)Leptin (ug/D)UntreatedTreated0vehicleleptin(0.1ug)leptin(1ug)vehicleleptin(0.1ug)leptin(1ug)UntreatedTreatedpAMPK levels in the hypothalamus by metformin treatment(Kim YW et al. Diabetes 55:716-724, 2006)
Page 1 and 2: β cell and Hyperglycemia in Type 2
Page 3 and 4: Schema of five stages of progressio
Page 5: GlucotoxicityChronic exposure to hi
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: Oxidative stressAdaptiveresponseEPO
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: 감사합니다

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