The fructosamine 3-kinase knockout mouse: a tool for testing the glycation hypothesis of intracellular protein damage in diabetes and aging.
Protein glycation and the formation of AGEs (advanced glycation end-products) and cross-links have been hypothesized to play a role in the pathogenesis of age- and diabetes-related complications. The discovery that FN3K (fructosamine 3-kinase) results in protein deglycation upon phosphorylation of glucose-derived Amadori products suggests that intracellular glycation could be deleterious under certain circumstances. In order to approach the question of the biological relevance of intracellular glycation, in this issue of the Biochemical Journal, Veiga-da-Cunha and colleagues generated an FN3K-knockout mouse. The mice grow normally and are apparently healthy, and levels of protein-bound and free fructoselysine are elevated in several tissues of importance to diabetic complications. This commentary discusses the clinical and evolutionary significance of FN3K, and proposes experimental approaches for revealing the existence of a biological phenotype.
Monnier
Vincent M
VM
Department of Pathology and Biochemistry, Case Western Reserve University, Cleveland, OH 44106, USA. vmm3@cwru.edu
D000375:Aging / Q000378:metabolism*; D000818:Animals; D003920:Diabetes Mellitus / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000172:deficiency* / Q000235:genetics
D017127:Glycation End Products, Advanced; D017853:Phosphotransferases (Alcohol Group Acceptor); C414347:fructosamine-3-kinase