The major role of liver glycogen is to supply glucose to the circulation maintaining the
normal blood glucose level. In 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 can be inhibited by glucose
and its analogues. Obviously, any readily accessible inhibitor of glycogen phosphorylase can be
used as a potential therapy of non-insulin-dependent or type 2 diabetes. Hepatic glycogen phosphorylase has been identified
as a new target for drugs that control blood glucose concentration. In our experiments glucopyranosylidene-spirothiohydantoin
(TH) was tested on the insulin sensitivity and blood glucose level of control and streptozotocin-treated rats.
The streptozotocin-treated rats failed to gain weight and exhibited stable hyperglycemia (4.7 ± 0.5 mmol/L glucose in
control vs. 7.8 ± 0.5 mmol/L) and low plasma insulin levels (9.6 ± 1.9 µIU/mL in control vs. 3.2 ± 2.2 µIU/mL). When insulin
supplementation with slow-release implants (2 IU/day) was started 8 weeks after streptozotocin injection, blood glucose
concentration remained suppressed, plasma insulin level dramatically increased and the insulin sensitivity restored.
TH administration significantly reduced the high blood glucose concentration and restored the insulin sensitivity of STZtreated
Keywords: Blood glucose, Glycogen phosphorylase inhibitor, Insulin implant, Streptozotocin, Type 2 diabetes.
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