[Relationship between adipose phosphoenolpyruvate carboxykinase and occurrence and reversion of insulin resistance].

OBJECTIVE: To investigate the relationship between the expression of phosphoenolpyruvate carboxykinase (PEPCK) gene and insulin resistance induced by high-fat diet and the effect of rosiglitazone, a thiazolidinedione drug.

METHODS: Sixty-three normal 8-week-old male SD rats were randomly divided into 2 groups: short-term group, n = 33, to be fed for 8 weeks and re-divide into 3 equal subgroups: standard chow diet subgroup (NC subgroup fed with standard chow diet), high-fat diet subgroup (HF subgroup, to be fed with lard), and high-fat diet with rosiglitazone subgroup (HF + rosiglitazone subgroup); and long-term group, n = 30, to be fed for 28 weeks, and re-divided into 3 corresponding 3 subgroups: By the end of experiment, serum samples were collected to examine the blood glucose (BG), triglyceride (TG) and free fatty acid (FFA). At the end of the experiment the rats were killed and the visceral adipose tissue was taken out to be weighed, and the liver, muscle, and epididymis were isolated. Glucose infusion rate (GIR) methods and tissue uptake of (3)H-2-deoxyglucose were used to short-and long-term groups evaluate the insulin sensitivity. PEPCK gene expression was investigated to detect the expression of PEPCK mRNA by using semi-quantitative RT-PCR method.

RESULTS: In the short-term group, the serum FFA and TG of the HF + rosiglitazone subgroup were lower by 24.5% and 54.0% respectively compared with those the HF subgroup (both P < 0.01). In the long-term group, the serum TG of the HF subgroup was higher by 32.4% in comparison with that of the NC subgroup (P < 0.05), and the serum FFA and TG of the HF + rosiglitazone subgroup were lower by 49.5% and 23.0% respectively compared with those of the HF subgroup (both P < 0.0). In the short-term group the GIR of the HF subgroup was lower by 51.25% in comparison with that of the NC subgroup (P < 0.01). And the GIR of the HF + rosiglitazone subgroup was higher by 149.6% than that of the HF group (P < 0.01). In the long-term group, the rate of uptake of (3)H-2-deoxyglucose in liver, muscle and adipose tissue of the HF subgroup were lower by 42.0%, 36.7%, and 48.1% respectively than those of the HF subgroup (all P < 0.01), and the rate of uptake of 3H-2-deoxyglucose in liver, muscle and adipose tissue of the HF + rosiglitazone subgroup were higher by 39.6%, 66.3%, and 66.7% respectively than those of the HF subgroup (all P < 0.01). In the short-term group the adipose PEPCK mRNA expression of the HF subgroup was 89% +/- 13% that of the NC subgroup; and the adipose PEPCK mRNA expression of the HF + rosiglitazone subgroup was 154% +/- 28% that of the NC subgroup, and was higher by 65.4% than that the HF subgroup (P < 0.05). In the long-term group, the adipose PEPCK mRNA expression of the HF + rosiglitazone subgroup was 144% +/- 17% that of the NC subgroup (P < 0.05), and was higher by 43.3% than that of the HF subgroup (P < 0.05).

CONCLUSION: Thiazolidinedione drug increases the re-esterification of fatty acids and reduces circulating FFA, and induces the expression of adipose PEPCK which is accompanied by reduction of FFA, thus improving insulin resistance.