EFFECTS OF REPEATED TREATMENTS WITH AN EXTRACT OF GINKGO-BILOBA (EGB-761) AND BILOBALIDE ON LIVER AND MUSCLE GLYCOGEN CONTENTS IN THE NON-INSULIN-DEPENDENT DIABETIC RAT
Jr. Rapin et al., EFFECTS OF REPEATED TREATMENTS WITH AN EXTRACT OF GINKGO-BILOBA (EGB-761) AND BILOBALIDE ON LIVER AND MUSCLE GLYCOGEN CONTENTS IN THE NON-INSULIN-DEPENDENT DIABETIC RAT, Drug development research, 40(1), 1997, pp. 68-74
The effects of repeated (15-day) oral treatments with an extract of Gi
nkgo biloba (EGb 761; 50 mg/kg/day) or with its terpenoid constituent,
bilobalide (2 mg/kg/day), were assessed in normal rats and in rats th
at had been previously injected with streptozotocin (50 mg/kg, i.p. in
saline solution), a dose which provided a model of non-insulin-depend
ent diabetes mellitus (NIDDM). In this model of diabetes, blood glucos
e is significantly increased while the circulating insulin level remai
ns unchanged. Glucose penetrates cells because of decreased glycogen t
urnover, a metabolic abnormality that can be revealed by using an oral
glucose tolerance test (OGTT). In control rats, hyperglycemia was acc
ompanied by increased glycogen synthesis, as evidenced by increased co
ncentrations of this storage substance in liver and skeletal muscle. R
epeated treatment with EGb 761 or bilobalide increased the glycogen co
ntents of both liver and muscle. This effect of bilobalide was additiv
e to that of hyperglycemia in muscle. In diabetic rats, hyperglycemia
did not modify glycogen synthesis, indicating impaired glucose utiliza
tion. Repeated treatment with EGb 761 or bilobalide partially prevente
d this impairment and led to increased in glycogen content in both liv
er and muscle under control conditions an during OGTT with 2 g/kg gluc
ose. The moleculasr mechanism underlying these actions of EGb 761 coul
d be related to an antioxidant effect (i.e., suppression of free radic
al formation) or to free radical-scavenging, since EGb 761 is known to
have such effects and since free radicals have been implicated in the
cytotoxic activity of streptozotocin. However, the increase in glucos
e uptake induced by bilobalide may have been related to increased glyc
ogen synthesis. (C) 1997 Wiley-Liss, Inc.