熊果酸通过过氧化物酶增殖受体α和γ信号通路改善KKAy小鼠肝脏胰岛素抵抗的机制

doi:10.3736/jcim20120710

Abstract

Objective: To explore the effects and mechanism of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes.
Methods: Thirty-five KKAy mice were divided into five groups according to the randomized block design, namely, control, rosiglitazone, fenofibrate, and high- and low-dose ursolic acid groups with seven mice in each group. C57BL/6J mice were used as the normal control group. At the end of the 4th week, free fatty acid (FFA), tumor necrosis factor-α (TNF-α) and adiponectin contents in serum were detected by enzyme-linked immunosorbent assay; the protein expressions of phosphoenolpyruvate carboxykinase (PEPCK), insulin receptor substrate-2 (IRS-2) and glucose transport factor-2 (GLUT-2) were detected by Western blot method; the mRNA expressions of PEPCK, IRS-2 and GLUT-2 were detected by real-time polymerase chain reaction; the expressions of peroxisome proliferator-activated receptor α (PPARα) and peroxisome proliferator-activated receptor γ (PPARγ) in liver tissue were detected by immunohistochemical method.
Results: After four weeks of intervention, the contents of FFA, TNF-α and adiponectin in serum of the high-dose ursolic acid group had changed, showing statistically significant difference compared to those of the control group (P<0.01); high dose of ursolic acid had depressant effect on the expressions of PEPCK protein and PEPCK mRNA (P<0.01); low dose of ursolic acid depressed the expression of PEPCK mRNA and induced phosphorylation of IRS-2 in the liver (P<0.05); both high and low dose of ursolic acid improved the expression of PPARα in the liver (P<0.01).
Conclusion: The effects of ursolic acid in improving hepatic insulin resistance in KKAy mice with spontaneous type 2 diabetes may be closely related to affecting the contents of FFA, TNF-α and adiponectin, improving the expression of PPARα protein, regulating transcription of PEPCK protein and inducing phosphorylation of IRS-2.

Key words: hypoglycemic agents (TCD), ursolic acid, PPARα, PPARγ, insulin resistance, diabetes mellitus, experimental, procetofen, mice

Lin Wang, Guan-liang Wang, Jia-han Liu, Di Li, De-zeng Zhu, Liang-neng Wu . Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ. Journal of Chinese Integrative Medicine, 2012, 10(7): 793-799.

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URL: http://www.jcimjournal.com/EN/10.3736/jcim20120710

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References 7

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Group	n	FFA (μmol/L)	TNF-α (ng/L)	Adiponectin (mg/L)
Normal	7	74.33±7.69^{**△△▲▲}	78.64±1.16^**	19.52±0.09^**△△
Control	7	427.32±9.31^▲▲	133.45±1.60^△△	4.13±0.12^▲▲
Rosiglitazone	7	352.68±9.15^▲▲	92.74±1.86^**	6.77±0.06^*
Fenofibrate	6	192.54±85.48^**△△	103.85±1.61^**	10.19±0.37^**△
UA 300 mL/(kg·d)	7	250.29±8.08^*△	105.42±1.27^*	6.82±0.10^▲
UA 150 mL/(kg·d)	6	341.45±151.41^▲▲	131.85±1.97^△△	5.79±0.05^▲

Group	n	PEPCK	GLUT-2	IRS-2
Normal	7	10.86±1.15^**	15.04±0.88^**	5.41±0.57^**
Control	7	18.37±1.29^△△	10.20±1.49	1.23±0.34
Rosiglitazone	7	12.45±1.26^**	11.63±0.83	1.63±0.17
Fenofibrate	6	15.97±1.47	13.59±0.95	1.34±0.12
UA 300 mL/(kg·d)	7	13.02±0.95^**△	11.15±1.33	2.38±0.27
UA 150 mL/(kg·d)	6	14.18±0.92^*	12.72±1.09	2.39±0.21

Group	n	PPARα	PPARγ
Normal	3	3.73±0.21^**	2.78±0.13
Control	3	1.53±0.15^▲▲	2.61±0.36
Rosiglitazone	3	1.84±0.26^▲	3.04±0.21
Fenofibrate	3	2.21±0.27^**△△	3.13±0.38
UA 300 mL/(kg·d)	3	3.10±0.34^**△△	2.72±0.07
UA 150 mL/(kg·d)	3	3.07±0.22^**△△	3.06±0.31

Effects of ursolic acid in ameliorating insulin resistance in liver of KKAy mice via peroxisome proliferator-activated receptors α and γ

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