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• There are ample evidences at the cellular level1) Glucotoxicity & oxidative stress : Glucose form ROS2) Pancreatic islets contain an usually low complement of antioxidantproteins and activity but normal γ -GCS expression3) Antioxidant drugs improve pancreatic islet survival in the face ofoxidative stress4) Gene transfer techniques can be used to overexpress antioxidantenzymes or HO-1 which provide enhanced protection of pancreaticbeta cells against oxidative stress5) At islets exposed to high glucose, high fatty acid may beexacerbating β cell dysfunction via increasing of CD 366) Because hyperglycemia is a prerequisite for lipotoxicity to occure,the term glucolipotoxicity, rather than lipotoxicity, is moreappropriate
• In human studies of type 2 diabetes1) Markers of oxidative stress are increased in type 2 diabetics2) Reducing plasma FFA levels may decrease the relative riskfor type 2 diabetes3) Glucolipotoxicity are secondary phenomena that areproposed to play a role in all forms of type 2 diabetes4) What new strategies might be utilized to protectthe β cell against glucolipotoxicity in type 2 diabetes ?: NAC ? GLP-1 ? DPP IV inhibitors ? etc…..
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 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: Summary
Page 67: 감사합니다
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