Unifying theory of diabetes complications by Michael Brownlee PhD says that excess fat or intracellular glucose causes excess electron carriers to be sent to the inner mitochondrial membrane; this leads to excess protons pumped into the intramembranous space (between OMM & IMM of mitochondria); this leads to REVERSAL of electron transport; which leads to CoEnzyme Q donating an electron to oxygen, to form superoxide anions (reactive oxygen species, also called “free radicals,” because have an unpaired electron in their outer shell). Superoxide anions generate a series of reactions that leads to DNA damage in the cell nucleus. DNA damage activates PARP (a DNA repair enzyme). PARP attaches an adenosyl-ribose group to the glycolysis enzyme called “GlycerAldehyde 3-phosphate DeHydrogenase,” which inhibits it. This blocks the glycolysis pathway. All the glycolysis substrates proximal (upstream) to this step begin to accumulate. In particular, GA-3-P is largely converted to DAG (Di Acyl Glycerol) = Glycerol attached to 2 fatty acids. DAG accumulation causes activation of Protein Kinase C (PKC). PKC causes insulin resistance, and has multiple other harmful effects. The key thing to learn from all this is that it is wise to minimize dietary fat. Populations with low fat diets, 10% or less dietary fat, hardly ever get type two diabetes.
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Diabetes complications, unifying theory, & how to avoid diabetes
