Effects of pioglitazone and/or simvastatin on circulating TNFα and adiponectin levels in insulin resistance

Figures & data

Table 1.  Time-dependent changes in body weight, glucose, insulin, and TG and TC in rats during 8 weeks of normal (NC) and high fructose diets (HFD).

Time (week)	Body weight (g)		Glucose (mg/dl)		Insulin (µIU)		TG (mg/dl)		TC (mg/dl)
	NC	HFD	NC	HFD	NC	HFD	NC	HFD	NC	HFD
0	120 ± 20	120 ± 20	78 ± 8	78 ± 8	14 ± 2	14 ± 2	82 ± 8	82 ± 8	77 ± 6	77 ± 6
4	200 ± 18*	250 ± 26*#	82 ± 11	120 ± 10*#	15 ± 3	20 ± 3*	85 ± 7	120 ±10*#	79 ± 5	100 ± 10*#
8	256 ± 25*	377 ± 20*#	81 ± 13	165 ± 15*#	15 ± 3	26 ± 2*#	90 ± 5	166 ± 10*#	80 ± 5	120 ± 14*#

Values are means ± SD (n = 10 rats/group).

Each group (NC and HFD) was compared with its ^*Week 0 value and with the ^#normal control at the same week. p< 0.05 (one-way ANOVA followed by Tukey post-hoc test). The data were gathered and used as a lead during the work.

Table 2.  Effect of 14-day oral PIO (10 mg/kg) and/or SIM (20 mg/kg) on serum glucose, insulin, HIRI, HbA1c, free fatty acid (FFA), and ALT.

Groups	Glucose (mg/dl)	Insulin (µIU)	HIRI	HbA1c (%)	FFA (mEq/L)	ALT (IU/L)
Control	80 ± 13	15 ± 2	3.0 ± 0.5	5.5 ± 0.2	0.36 ± 0.05	26 ± 7
HFD	163 ± 15*	26 ± 2*	11.0 ± 2.0*	7.0 ± 0.3*	0.67 ± 0.06*	62 ± 6*
HFD/PIO	120 ± 18*#	19 ± 2*#	5.0 ± 0.4*#	5.0 ± 0.5#	0.55 ± 0.04*#	46 ± 5*#
HFD/SIM	160 ± 28*	22 ± 1*	8.0 ± 2.0*#	6.0 ± 0.3*	0.50 ± 0.06*#	47 ± 5*#
HFD/PIO+SIM	93 ± 12#^a^b	15 ± 2#^a^b	3.0 ± 0.2#^a^b	4.0 ± 0.6*#^b	0.42 ± 0.04*#^a^b	40 ± 3*#^a^b

All rats were provided normal chow or HFD for 8 weeks prior to 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). Values shown are mean ± SD (n = 10 rats/group).

^‡Value shown is 100× the actual ratio of parameter/BW.

^*#Value significantly different from normal control and HFD, respectively, at p < 0.05.

^a,bValue significantly different compared with PIO and SIM groups, respectively, at p < 0.05.

Figure 1.  (a) Glucose tolerance curve of normal and insulin resistant rats after initial 8 weeks on the HFD alone and then 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). (b) Changes in the area under the curve (AUC) as derived from the glucose tolerance test for normal control, non-drug-treated HFD, and drug-treated HFD rats. Values shown are mean ± SD (n = 10 rats/group).*^,# Value significantly different compared with normal control and HFD control, respectively, at p < 0.05.*^{,# a,b} Value significantly different compared with PIO or SIM group, respectively, at p< 0.05.^a,b Values shown are mean ± SD (n = 10 rats per each group).

Figure 2.  Effect of 14-day oral PIO (10 mg/kg) and/or SIM (20 mg/kg) on serum triglyceride (TG), total cholesterol (T-Chol), LDL (LDL-C), and HDL. All rats were provided normal chow or HFD for 8 weeks prior to 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). Values shown are mean ± SD (n = 10 rats/group).*^,# Value significantly different compared with normal control and HFD, respectively, at p < 0.05.^a,bValue significantly different compared with PIO or SIM group, respectively, at p< 0.05.

Table 3.  Effect of 14-day oral PIO (10 mg/kg) and/or SIM (20 mg/kg) on hepatic TG content and of epididymal fat:, visceral fat:, and liver weight:BW ratios.

Groups	Hepatic TG (mg/100 mg protein)	Epididymal fat:BW^‡	Visceral fat:BW^‡	Liver wt:BW^‡
Control	8 ± 1	0.70 ± 0.05	0.74 ± 0.03	3.00 ± 0.17
HFD	45 ± 5*	1.00 ± 0.01*	1.00 ± 0.09*	3.80 ± 0.20*
HFD/PIO	35 ± 3*#	0.90 ± 0.07*#	0.72 ± 0.08#	3.20 ± 0.15*#
HFD/SIM	27 ± 3*#	0.80 ± 0.06*#	0.70 ± 0.06#	3.20 ± 0.20*#
HFD/PIO+SIM	25 ± 2*#^a	0.60 ± 0.05*#^a^b	0.68 ± 0.05#^a	3.30 ± 0.20*#

All rats were provided normal chow or HFD for 8 weeks prior to 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). Values shown are mean ± SD (n = 10 rats/group).

^‡Value shown is 100× the actual ratio of parameter/BW.

^*#Value significantly different from normal control and HFD, respectively, at p < 0.05.

^a,bValue significantly different compared with PIO and SIM groups, respectively, at p < 0.05.

Figure 3.  Effect of 14-day oral PIO (10 mg/kg) and/or SIM (20 mg/kg) on serum TNFα. All rats were provided normal chow or HFD for 8 weeks prior to 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). Values shown are mean ± SD (n = 10 rats/group). Value significantly different compared with normal control and HFD, respectively, at p < 0.05. ^{*,# a, b}Value significantly different compared with PIO or SIM group, respectively, at p < 0.05.

Figure 4.  Effect of oral PIO (10 mg/kg) and/or SIM (20 mg/kg) on serum Adp. All rats were provided normal chow or HFD for 8 weeks prior to 14 days on the indicated treatment drug (in conjunction with maintenance of HFD). Values shown are mean ± SD (n = 10 rats/group). *,# Value significantly different compared with normal control and HFD, respectively, at p < 0.05. Value significantly different compared with PIO or SIM group, respectively, at p < 0.05.^{a, b} Value significantly different compared with PIO or SIM group, respectively, at p < 0.05.

Table 4.  Correlation coefficient (r) for TNFα and Adp (as well as HIRI) with FFA, HIRI, hepatic TG, and visceral fat.

Correlations	FFA	HIRI	Hepatic TG	Visceral fat ratio	TNFα
HIRI	r = +0.905*	—	r = +0.787*	r = +0.708*	r = +0.872*
Adp	r = –0.454*	r = –0.689*	r = –0.164	r = –0.597*	r = –0.312
TNFα	r = +0.905*	r = +0.872*	r = +0.950*	r = +0.564*	—

Correlational analyses were carried out in treated and untreated resistant animals rats using linear regression analysis. Statistical significance (*) was taken at p < 0.01.