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. 2014 Sep;47(9):780-8.
doi: 10.1590/1414-431x20142983. Epub 2014 Jul 25.

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

R M Banin  1 , B K S Hirata  1 , I S Andrade  2 , J C S Zemdegs  2 , A P G Clemente  3 , A P S Dornellas  2 , V T Boldarine  2 , D Estadella  4 , K T Albuquerque  5 , L M Oyama  2 , E B Ribeiro  2 , M M Telles  1
Affiliations

Beneficial effects of Ginkgo biloba extract on insulin signaling cascade, dyslipidemia, and body adiposity of diet-induced obese rats

R M Banin et al. Braz J Med Biol Res. 2014 Sep.

Abstract

Ginkgo biloba extract (GbE) has been indicated as an efficient medicine for the treatment of diabetes mellitus type 2. It remains unclear if its effects are due to an improvement of the insulin signaling cascade, especially in obese subjects. The aim of the present study was to evaluate the effect of GbE on insulin tolerance, food intake, body adiposity, lipid profile, fasting insulin, and muscle levels of insulin receptor substrate 1 (IRS-1), protein tyrosine phosphatase 1B (PTP-1B), and protein kinase B (Akt), as well as Akt phosphorylation, in diet-induced obese rats. Rats were fed with a high-fat diet (HFD) or a normal fat diet (NFD) for 8 weeks. After that, the HFD group was divided into two groups: rats gavaged with a saline vehicle (HFD+V), and rats gavaged with 500 mg/kg of GbE diluted in the saline vehicle (HFD+Gb). NFD rats were gavaged with the saline vehicle only. At the end of the treatment, the rats were anesthetized, insulin was injected into the portal vein, and after 90s, the gastrocnemius muscle was removed. The quantification of IRS-1, Akt, and Akt phosphorylation was performed using Western blotting. Serum levels of fasting insulin and glucose, triacylglycerols and total cholesterol, and LDL and HDL fractions were measured. An insulin tolerance test was also performed. Ingestion of a hyperlipidic diet promoted loss of insulin sensitivity and also resulted in a significant increase in body adiposity, plasma triacylglycerol, and glucose levels. In addition, GbE treatment significantly reduced food intake and body adiposity while it protected against hyperglycemia and dyslipidemia in diet-induced obesity rats. It also enhanced insulin sensitivity in comparison to HFD+V rats, while it restored insulin-induced Akt phosphorylation, increased IRS-1, and reduced PTP-1B levels in gastrocnemius muscle. The present findings suggest that G. biloba might be efficient in preventing and treating obesity-induced insulin signaling impairment.

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Figures

Figure 1
Figure 1. Body mass of normal fat diet (NFD; n=16) and high-fat diet (HFD; n=71) groups during obesity-induction period. *P<0.05 vs NFD (Student t-test).
Figure 2
Figure 2. A, Food intake (g·100 g-1·24 h-1) and B, energy intake (kcal·100 g-1·24 h-1) of normal fat diet (NFD; n=16) and high-fat diet (HFD; n=71) groups during obesity-induction period. *P<0.05 vs NFD (Student t-test).
Figure 3
Figure 3. A, Cumulative food intake (g) and B, cumulative energy intake (kcal/100 g) of normal fat diet (NFD; n=12), high-fat diet plus vehicle (HFD+V; n=25), and high-fat diet plus Ginkgo biloba (HFD+Gb; n=20) groups during phytotherapy treatment. *P<0.05 vs NFD, #P<0.05 vs HFD+V (one-way ANOVA followed by the Tukey HSD test).
Figure 4
Figure 4. Mass weight (g) of retroperitoneal, epididymal and mesenteric white adipose tissue depots of normal fat diet (NFD; n=16), high-fat diet plus vehicle (HFD+V; n=11), and high-fat diet plus Ginkgo biloba (HFD+Gb; n=9) groups after phytotherapy. *P<0.05 vs NFD, #P<0.05 vs HFD+V (one-way ANOVA followed by the Tukey HSD test).
Figure 5
Figure 5. Insulin tolerance test (ITT) of normal fat diet (NFD; n=11), high-fat diet plus vehicle (HFD+V; n=6), and high-fat diet plus Ginkgo biloba (HFD+Gb; n=6) groups after phytotherapy treatment. *P<0.05 vs NFD; #P<0.05 vs HFD+Gb (two-way ANOVA - time vs phytotherapy treatment - followed by Tukey HSD post hoc analysis).
Figure 6
Figure 6. Akt phosphorylation levels in gastrocnemius muscle of A, NFD- (basal, n=5) and NFD+ (insulin-stimulated, n=5); B, HFD+V- (basal, n=6) and HFD+V+ (insulin-stimulated, n=6); and C, HFD+Gb- (basal, n=6) and HFD+Gb+ (insulin-stimulated, n=6) groups after phytotherapy treatment. Akt: protein kinase B; NFD: normal fat diet; HFD: high-fat diet; V: vehicle (saline); Gb: Ginkgo biloba. *P<0.05 vs basal (Student t-test).
Figure 7
Figure 7. IRS-1 levels in gastrocnemius muscle of NFD (n=10), HFD+V (n=7), and HFD+Gb (n=9) groups after phytotherapy treatment. IRS-1: insulin receptor substrate 1; NFD: normal fat diet; HFD: high-fat diet; V: vehicle (saline); Gb: Ginkgo biloba. #P<0.05 vs HFD+V (one-way ANOVA followed by the Tukey HSD test).
Figure 8
Figure 8. PTP-1B levels in gastrocnemius muscle of NFD (n=10), HFD+V (n=9), and HFD+Gb (n=8) groups after phyttherapy treatment. PTP-1B: protein tyrosine phosphatase 1B; NFD: normal fat diet; HFD: high-fat diet; V: vehicle (saline); Gb: Ginkgo biloba. #P<0.05 vs HFD+V (one-way ANOVA followed by the Tukey HSD test).
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