Effect of Berberine on the Insulin Resistance and TLR4/IKKβ/NF-κB Signaling Pathways in Skeletal Muscle of Obese Rats with Insulin Resistance

HOU Li-qiong, ZHAO Tie-yun, ZHANG Yi-yi

Abstract

To investigate the role of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) signaling pathway for umbilical cord-derived mesenchymal stem cells (UC-MSCs) treating in neonatal rats with hypoxia-ischemia brain damage (HIBD). Methods P10 SD rats were divided into sham group, MSCs group, inhibitor (LY 294002) group (LY group) and HIBD group randomly. To establish a neonatal rat model of HIBD, UC-MSCs labeled with Brd U were transplanted into the lateral ventricle of rats. At 24 and 48 h after transplantation, the number of apoptotic cells was detected by TUNEL, while the expression of caspase3 protein and phosphorylation of Akt (P-Akt) were quantified by Western blot. Results At 24 and 48 h after transplantation, both the apoptotic cells and caspase3 protein expression in MSCs group were less than those in LY group and HIBD group ( P<0.05), while the expression of P-Akt was higher than those in LY group and HIBD group ( P<0.05), and with the passage of time after transplantation, the expression of each index showed a downward trend. Conclusion The apoptotic cells of brain and the expression of caspase3 protein decrease, while the expression of P-Akt increase. PI3K/Akt signaling pathway may be an important mechanism for UC-MSCs transplantation in HIBD rats.

 

Keywords: Berberine, Skeletal muscle Insulin resistance, TLR4 IKKβ 

 

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References


Cani PD. Bibiloni R, Knauf C. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice . Diabetes,2008;57(6): 1470-1181.

Gu JJ, Gao FY. Zhao TY. A preliminary investigation of the mechanisms underlying the effect of berberine in preventing high-fat diet-induced insulin resistance in rats. J Physiol Pharmacol,2012;63 (5):505-513.

Chen Y. Li Y. Wang Y. et al. Berberine improves free-fatty-acid- induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor gamma and fatty acid transferase expressions. Metabolism,2009;58(12): 1694-1702.

Oliveira AG, Carvalho BM, Tobar N, et al. Physical exercise reduces circulating lipopolysaccharide and TLR4 activation and improves insulin signaling in tissues of DIO rats. Diabetes,2011 ;60 (3): 784-796.

Yi P , Lu FE, Xu LJ , et al . Berberine reverses free-fatty-acid- induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta. World J Gastroenterol.2008; 14(6);876-883.

Areias MF. Prada PO. Mechanisms of insulin resistance in the amygdala: influences on food intake. Behav Brain Res, 2015; 282 (0 : 209-217.

Guo S. Insulin signaling, resistance, and the metabolic syndrome; insights from mouse models into disease mechanisms. J Endocrinol, 2014;220(2): 1-23.

Hojlund K. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance. Dan Med J,2014;61(7); B4890.

Jiang Y. Biswas SK. Serine 307 on insulin receptor substrate 1 is required for SOCS3 and TNF-alpha signaling in the rMC-1 cell line. Mol Vis,2014;20(l): 1463-1470.

Radin M. Sin ha S , Bhatt B, et al. Inhibition or deletion of the lipopolysaecharide receptor Toll-like receptor-4 confers partial protection against lipid-induced insulin resistance in rodent skeletal muscle. Diabetologia. 2008; 51 (2): 336-346.

Suganami T, Tanimoto-Koyama K. Nishida J, et al. Role of the Toll-like receptor 4/NF-kappaB pathway in saturated fatty acid- induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vase Biol.2007;27(1):84- 91.

Zhang J. Wu W. Li D, et al. Overactivation of NF-kappaB impairs insulin sensitivity and mediates palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Endocrine, 2010;37С1): 157-166.

Solinas G. Karin M. JNK1 and IKK{3: molecular links between obesity and metabolic dysfunction. FASEB J, 2010; 24 ( 8 ): 2596- 2611.


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