Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Non-enzymatic glycosylation of proteins, also called Maillard reaction, which occurs at an accelerated rate in diabetes, can lead to the formation of advanced glycosylation endproducts (AGEs). Tenilsetam (CAS 997: (+/-)-3-(2-thienyl)-2-piperazinone), a cognition-enhancing drug successfully used for treatment of patients suffering from Alzheimer's disease, when included in the Maillard reaction apparently inhibits protein crosslinking by AGEs in vitro. According to the mechanism proposed, Tenilsetam acts via covalent attachment to glycated proteins, thus blocking the reactive sites for further polymerisation reactions. A beneficial effect of Tenilsetam in Alzheimer's disease could come from the interference with AGE-derived crosslinking of amyloid plaques and a decreased inflammatory response by diminished activation of phagocytosing microglia.
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PMID:The cognition-enhancing drug tenilsetam is an inhibitor of protein crosslinking by advanced glycosylation. 774 63

It has been hypothesized that advanced Maillard reaction in vivo could explain some of the age- and diabetes-related changes. Furthermore, involvement of the Maillard reaction with Alzheimer's disease has also been suggested, as advanced glycation end products, such as pyrraline and pentosidine, were demonstrated to localize in lesions of the disease. Although aminoguanidine has been studied extensively and established as an inhibitor of the Maillard reaction, other candidates have not been investigated thoroughly. In the present study, we examined the inhibitory effect of tenilsetam [(+/-)-3-(2-thienyl)-2-piperazinone], an antidementia drug, on the Maillard reaction. Tenilsetam inhibited glucose- and fructose-induced polymerization of lysozyme in a concentration-dependent manner in vitro. Reduced enzymatic digestibility of collagen incubated with 100 mM glucose for 4 weeks was also restored to a control level by coincubation with 100 mM tenilsetam. To determine whether tenilsetam inhibits the Maillard reaction in vivo, streptozotocin-induced diabetic rats were treated with tenilsetam (50 mg/kg x day). Elevated levels of advanced glycation end-product-derived fluorescence and pyrraline in renal cortex and aorta of diabetic rats were suppressed by the administration of tenilsetam for 16 weeks. These inhibitory effects of this agent on advanced glycation in diabetic rats suggested its potential therapeutic role in controlling diabetic complications.
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PMID:Inhibitory effects of tenilsetam on the Maillard reaction. 911 83