Yallow and Berson found high serum insulin in type diabetes, thus insulin resistance : common underlying biochemical abnormality



Yüklə 513 b.
tarix29.10.2017
ölçüsü513 b.
#19721







1. Yallow and Berson found high serum insulin in type 2 diabetes, thus insulin resistance : common underlying biochemical abnormality

  • 1. Yallow and Berson found high serum insulin in type 2 diabetes, thus insulin resistance : common underlying biochemical abnormality

  • 2. Molecular approach (insulin receptor and post-receptor mechanisms) was not successful

  • 3. Epidemiologic approach by establishing a disease entity (syndrome X) proposed by Reaven (1988)

  • 4. WHO experts gave new name; metabolic syndrome (1998)





Genetic cause (thrifty genotype hypothesis. Neel JV, 1962)

  • Genetic cause (thrifty genotype hypothesis. Neel JV, 1962)

  • Fetal malnutrition (thrifty phenotype hypothesis. Barker DJP and Hales CN, 1992)

  • 3 Mitochondrial dysfunction (Lee HK et al, 2006)

  • Environmental chemicals (Baillie-Hamilton PF, 2002) and POPs (Lee DH et al, 2006)







As genes did not change, something in the environment should have caused it

  • As genes did not change, something in the environment should have caused it

  • Causative agent(s) should be not infectious

  • Introduced by industrialization/ westernization/ coca-cola-rization?

  • Diabetogenic drug, streptozotocin damaged cell as NO donor

  • Mitochondrion is most vulnerable target of free radicals



mtDNA 0.41 +/- 0.06 (n = 12) pmol of 8-OHdG per ug

  • mtDNA 0.41 +/- 0.06 (n = 12) pmol of 8-OHdG per ug

  • nDNA 0.025+/- 0.004 (n = 4)

  • 16 times lower level of 8-OHdG in nuclear DNA

  • Oxidative damage should leave clue in mtDNA

  • What the hell is mitochondria and its DNA?



mtDNA density decrease precede the development of diabetes in Yochon cohort, 1998

  • mtDNA density decrease precede the development of diabetes in Yochon cohort, 1998

  • Medical student cohort (KU Lee et al)

  • Birth weight and mtDNA density (YY Lee, YA Sung): thrifty phenotype hypothesis

  • mtDNA variations and insulin resistance (Asians)

  • 16189 T>C,

  • haplogroups N9a (resistant)

  • haplogroups B and F (sensitive)

  • (In collaboration with M Tanaka et al, K Nanjo et al)



















Genetic cause (thrifty genotype hypothesis. Neel JV, 1962)

  • Genetic cause (thrifty genotype hypothesis. Neel JV, 1962)

  • Fetal malnutrition (thrifty phenotype hypothesis. Barker DJP and Hales CN, 1992)

  • 3 Mitochondrial dysfunction (Lee HK et al, 2006)

  • Environmental chemicals (Baillie-Hamilton PF, 2002) and POPs (Lee DH et al, 2006)























This association was confirmed in Greenland (Inuit), Taiwan, Japan, Native American, Slovakia and Belgium (Dirink E et al. Obesity, 2010).

  • This association was confirmed in Greenland (Inuit), Taiwan, Japan, Native American, Slovakia and Belgium (Dirink E et al. Obesity, 2010).

  • An environment-wide association study (EWAS) on type 2 diabetes mellitus supported (Chirag J et al, PLoS One 2010)

  • Confirmed in experimental studies (Lim S, PLoS One, 2009; Ruzzin J et al, Environ Health Persp, 2009)





























Establishing cause-effect relationship between xenobiotics exposure and MS

  • Establishing cause-effect relationship between xenobiotics exposure and MS

  • 3 Koch’s postulates

  • Etiologic treatment: drug development and clinical trials



POPs are very diverse, small, slowly act, dangerous to handle and ---

  • POPs are very diverse, small, slowly act, dangerous to handle and ---

  • Current detecting methods are too expensive

  • Need cheap and valid method (for diagnosis): i.e. CALUX (chemically activated luciferase expression) assay

  • Best way to eliminate toxins (evidence-based detoxification therapy)









Park KS, Cho YM, Lim S, KimPak Y, Lee W, and many collaborators, Korea

  • Park KS, Cho YM, Lim S, KimPak Y, Lee W, and many collaborators, Korea

  • Wei Y-H, Taiwan

  • Nanjo K, Tanaka M. Japan

  • Members of Molecular Diabetology in Asia




Yüklə 513 b.

Dostları ilə paylaş:




Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©muhaz.org 2022
rəhbərliyinə müraciət

    Ana səhifə