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May 7, 2006
Good Diabetes Review Article
Michael Brownlee wrote an excellent review article in Nature in 2001 (414:813-820), Biochemistry and Molecular Cell Biology of Diabetic Complications. It talks about AGEs, sorbitol and the polyol pathway, reactive oxygen species, glutathione and free radicals, the hexosamine pathway, protein kinase C (PKC), and offers that a high mitochondrial membrane potential might play a central role in all of these. The excess glucose raises the mitochondrial membrane potential, but this is converted to heat by thermogenin (uncoupling protein-1), until thermogenin is overwhelmed. Brownlee argues that it is only when thermogenin is overwhelmed that the glucose becomes so great that it starts backing up into these other pathways (polyols, hexosamines, AGEs, and PKC activation). Just gotta get over the British spelling of hyperglycaemia.
What the others do:
Polyol pathway: increases sorbitol, causing damage.
AGEs: inhibit proper protein function, particularly among structural proteins.
Hexosamine pathway: creates glycoproteins
PKCs: activate lots of processes involved with making new vessels and laying down fibrous proteins, but also inhibits nitric oxide synthesis in capillaries and kidney glomeruli, so these vessels don't dialate. Also causes increased vessel permeability via VEGF.
And I really hate it when I make additions to the Wikipedia but forget to sign in before they're recorded.
Posted by Niels Olson at May 7, 2006 8:20 PM
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