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Research Article

Metformin attenuates hepatic insulin resistance in type-2 diabetic rats through PI3K/Akt/GLUT-4 signalling independent to bicuculline-sensitive GABAA receptor stimulation

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Pages 722-728 | Received 01 Sep 2015, Accepted 30 Nov 2016, Published online: 31 Jan 2017

Figures & data

Table 1. Effect of metformin in presence/absence of bicuculline or wortmannin on T2DM-induced changes in plasma glucose level of T2DM rats in OGTT.

Table 2. Effect of metformin in presence/absence of bicuculline or wortmannin on T2DM-induced changes in the plasma glucose level of T2DM rats in ITT.

Table 3. Effect of metformin in presence/absence of bicuculline or wortmannin on T2DM-induced changes in the fasting blood glucose and insulin level, HOMA-IR and HOMA-B indices of T2DM rats.

Figure 1. The effect of metformin in presence/absence of bicuculline or wortmannin on T2DM-induced changes in the level of hepatic intracellular calcium. All values are mean ± SEM (n = 6). ap < 0.05 compared to control, bp < 0.05 compared to T2DM, cp < 0.05 compared to T2DM + MET dp < 0.05 compared to T2DM + MET + BIC and ep < 0.05 compared to T2DM + MET + WAT (one-way ANOVA followed by Student–Newman–Keuls test).

Figure 1. The effect of metformin in presence/absence of bicuculline or wortmannin on T2DM-induced changes in the level of hepatic intracellular calcium. All values are mean ± SEM (n = 6). ap < 0.05 compared to control, bp < 0.05 compared to T2DM, cp < 0.05 compared to T2DM + MET dp < 0.05 compared to T2DM + MET + BIC and ep < 0.05 compared to T2DM + MET + WAT (one-way ANOVA followed by Student–Newman–Keuls test).

Figure 2. The effect of metformin in presence/absence of bicuculline or wortmannin on the level of expression of Akt (B) and p-Akt (C), and ratio of p-Akt to Akt (D) in liver of T2DM rats. The blots are representative of Akt and p-Akt in liver (A). The results in the histogram are expressed as the ratio of relative intensity of levels of expression of Akt or p-Akt to β-actin. All values are mean ± SEM of three separate sets of independent experiments. ap < 0.05 compared to control, bp < 0.05 compared to T2DM and cp < 0.05 compared to T2DM + MET [One-way ANOVA followed by Student–Newmann–Keuls post-hoc test].

Figure 2. The effect of metformin in presence/absence of bicuculline or wortmannin on the level of expression of Akt (B) and p-Akt (C), and ratio of p-Akt to Akt (D) in liver of T2DM rats. The blots are representative of Akt and p-Akt in liver (A). The results in the histogram are expressed as the ratio of relative intensity of levels of expression of Akt or p-Akt to β-actin. All values are mean ± SEM of three separate sets of independent experiments. ap < 0.05 compared to control, bp < 0.05 compared to T2DM and cp < 0.05 compared to T2DM + MET [One-way ANOVA followed by Student–Newmann–Keuls post-hoc test].

Figure 3. The effect of metformin in presence/absence of bicuculline or wortmannin on the level of expression of cytoplasmic (B) and membranous (C), and ratio of p-membranous to cytoplasmic (D) GLUT-4 in liver of T2DM rats. The blots are representative of cytoplasmic and membranous (A) GLUT-4 in liver. The results in the histogram are expressed as the ratio of relative intensity of levels of expression of cytoplasmic or membranous GLUT-4 to β-actin. All values are mean ± SEM of three separate sets of independent experiments. ap < 0.05 compared to control, bp < 0.05 compared to T2DM and cp < 0.05 compared to T2DM + MET [One-way ANOVA followed by Student–Newmann–Keuls post hoc test].

Figure 3. The effect of metformin in presence/absence of bicuculline or wortmannin on the level of expression of cytoplasmic (B) and membranous (C), and ratio of p-membranous to cytoplasmic (D) GLUT-4 in liver of T2DM rats. The blots are representative of cytoplasmic and membranous (A) GLUT-4 in liver. The results in the histogram are expressed as the ratio of relative intensity of levels of expression of cytoplasmic or membranous GLUT-4 to β-actin. All values are mean ± SEM of three separate sets of independent experiments. ap < 0.05 compared to control, bp < 0.05 compared to T2DM and cp < 0.05 compared to T2DM + MET [One-way ANOVA followed by Student–Newmann–Keuls post hoc test].