title: Effect of glucopyranosylidene-spiro-thiohydantoin on glycogen metabolism in liver tissues of streptozotocin-induced and obese diabetic rats.
abstract: The major role of liver glycogen is to supply glucose to the circulation in order to maintain normal blood glucose levels. In the muscle and liver, the accumulation and breakdown of glycogen are regulated by the reciprocal activities of glycogen phosphorylase and glycogen synthase. Glycogen phosphorylase catalyses the key step of glycogen degradation and its activity is inhibited by glucose and its analogues. Thus, any readily accessible inhibitor of glycogen phosphorylase may serve as a potential therapy for non-insulin-dependent or type 2 diabetes. Hepatic glycogen phosphorylase has been identified as a novel target for drugs that control blood glucose concentration. Glucopyranosylidene-spiro-thiohydantoin (TH) was found to be one of the most potent glucose derivates, inhibiting the catalytic activity of both muscle and liver glycogen phosphorylase. Here, we demonstrated the co-ordinated regulation of glycogen phosphorylase and synthase by 50 µM TH in liver extracts of Wistar rats, resulting in the activation of synthase by a shortening of the latency compared to control animals. TH was also effective in lowering blood glucose levels and restoring hepatic glycogen content in streptozotocin-induced diabetic rats. Furthermore, intravenous administration of TH to Zucker diabetic fatty rats significantly decreased hepatic glycogen phosphorylase a levels, and the activation of synthase was initiated without any delay.
authors.affiliation: Cell Biology and Signalling Research Group of the Hungarian academy of Sciences, Debrecen, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.forename: Katalin
authors.initials: K
authors.lastname: Czifrák
authors.forename: Csaba
authors.initials: C
authors.lastname: Hüse
authors.forename: László
authors.initials: L
authors.lastname: Somsák
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006003:Glycogen / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000378:metabolism; D006006:Glycogen Synthase / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009005:Monosaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D013141:Spiro Compounds / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D009005:Monosaccharides; D013141:Spiro Compounds; C452302:glucopyranosylidene spirothiohydantoin; D006003:Glycogen; D024981:Glycogen Phosphorylase; D006006:Glycogen Synthase