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

Abstract

The effects of repeated (15-day) oral treatments with an extract of Ginkgo 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 that had been previously injected with streptozotocin (50 mg/kg, i.p. in saline solution), a dose which provided a model of non-insulin-dependent diabetes mellitus (NIDDM). In this model of diabetes, blood glucose is significantly increased while the circulating insulin level remains unchanged. Glucose penetrates cells because of decreased glycogen turnover, a metabolic abnormality that can be revealed by using an oral glucose tolerance test (OGTT). In control rats, hyperglycemia was accompanied by increased glycogen synthesis, as evidenced by increased concentrations of this storage substance in liver and skeletal muscle. Repeated treatment with EGb 761 or bilobalide increased the glycogen contents of both liver and muscle. This effect of bilobalide was additive to that of hyperglycemia in muscle. In diabetic rats, hyperglycemia did not modify glycogen synthesis, indicating impaired glucose utilization. Repeated treatment with EGb 761 or bilobalide partially prevented this impairment and led to increased in glycogen content in both liver and muscle under control conditions an during OGTT with 2 g/kg glucose. The moleculasr mechanism underlying these actions of EGb 761 could be related to an antioxidant effect (i.e., suppression of free radical 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 glucose uptake induced by bilobalide may have been related to increased glycogen synthesis. Drug Dev. Res. 40:68-74, 1997.

Ginkgo biloba extract modifies hypoglycemic action of tolbutamide via hepatic cytochrome P450 mediated mechanism in aged rats

“…Considering these situations and the efficacy of GBE reported so far (Iliff and Auer, 1983;Lanthony and Cosson, 1988;Doly et al, 1992;Rapin et al, 1997), the simultaneous intake of GBE and anti-diabetic drug is most likely to occur in the elderly. For the safe use of both GBE and drugs, it is important to elucidate how GBE taken as a dietary supplement modifies the efficacy of therapeutic drugs.…”

“…In particular, GBE has been shown to improve peripheral blood flow (Iliff and Auer, 1983) and is expected to prevent periphery necrosis and retinopathy in severe diabetes (Lanthony and Cosson, 1988;Doly et al, 1992). It is also reported that GBE inhibits the increment of blood glucose concentration in glucose-loaded diabetic rats (Rapin et al, 1997). Thus, the simultaneous intake of GBE and anti-diabetic agents might occur, particularly in elderly people.…”

Involvement of Ca2+, CaMK II and PKA in EGb 761-induced insulin secretion in INS-1 cells

“…Several reports showed that Ginkgo extract reduced blood glucose (Rapin et al, 1997;Shankar et al, 2005;Tanaka et al, 2004). But, reduction mechanism of blood glucose was not consistent.…”

“…But, reduction mechanism of blood glucose was not consistent. Ginkgo extract lowered blood glucose via insulin-like action (Rapin et al, 1997), antioxidant activity (Shankar et al, 2005) or inhibitory effect of glucosidase (Tanaka et al, 2004). Especially, Kudolo reported that Ginkgo extract increased pancreatic beta-cell function in healthy subjects and in type 2 diabetic subjects with pancreatic exhaustion (Kudolo, 2000(Kudolo, , 2001 although the same treatment of Ginkgo extract produced no significant effect on beta-cell function in hyperinsulinemic type 2 diabetic subjects (Kudolo, 2001).…”

“…In addition to its neuro-and vascular protective effects, EGb 761 has been reported to reduce hyperglycemia. Rapin et al (1997) reported that EGb 761 elevated glucose uptake and glycogen synthesis and Tanaka et al (2004) showed that the glucose-lowering effect of Ginkgo extracts is due to their inhibitions of alpha-amylase and glucosidase. Kudolo (2001) reported that 3-month EGb 761 ingestion could increase plasma insulin levels by oral glucose tolerance testing in type 2 diabetic subject with pancreatic exhaustion and thus suggested that EGb 761 increased pancreatic beta-cell function.…”