Berberine (BBR), a natural compound extracted from a Chinese herb, has been shown to effectively attenuate insulin resistance (IR) and inflammation in the clinic. However, its ameliorative mechanism against IR is not well defined. This study is aimed at investigating the effect of BBR and protein phosphatase, Mg²⁺/Mn²⁺-dependent 1B (PPM1B) on IR. Biochemical measurements and liver histopathology were detected using the biochemical analyzer and HE staining in ZDF rats, respectively. Microarray analysis of liver tissues was performed, and differentially expressed gene (DEG) levels were examined by quantitative real-time PCR (qPCR) and Western blot. Additionally, the effect of BBR was also explored in HepG2-IR cells. The glucose oxidase method and the fluorescent glucose analog were used to detect glucose consumption and uptake, respectively. The PKA inhibitor H89, ELISA, qPCR, Western blot, and immunofluorescence staining were employed to estimate the expression levels of related signaling pathways. To evaluate the roles of PPM1B, HepG2-IR cells were stably infected with lentivirus targeting PPM1B. The administration of BBR drastically decreased the body weight, urine volume, blood glucose, blood urea nitrogen (BUN), CHOL, hepatic index levels, and pathologic changes and improved ALB levels in ZDF rats with PPM1B upregulation. Furthermore, BBR effectively improves glucose consumption, uptake, and inflammation in HepG2-IR cells. The knockdown of PPM1B expression aggravated the inflammatory response and glycometabolism disorder in HepG2-IR cells. Mechanistically, a reversal in the expression of cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKβ Ser181, IKKβ, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 contributes to ameliorate IR in HepG2-IR cells with BBR treatment. Altogether, these results suggest that BBR might regulate IR progression through the regulation of the cAMP, PKA, PPM1B, PPARγ, LRP1, GLUT4, NF-κB p65, JNK, pIKKβ Ser181, IKKβ, IRS-1 Ser307, IRS-1, IRS-2 Ser731, IRS-2, PI3K p85, and AKT Ser473 expression in the liver.

中文翻译：

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小ber碱通过PPM1B途径改善Zucker糖尿病大鼠和胰岛素抵抗性HepG2细胞中糖尿病的炎症反应。

小ber碱（BBR）是一种从中草药中提取的天然化合物，已被证明可有效减轻临床上的胰岛素抵抗（IR）和炎症。但是，其针对IR的改善机制尚未明确定义。本研究旨在研究BBR和蛋白磷酸酶Mg ²⁺ / Mn ^2+的作用依赖于IR的1B（PPM1B）。使用生化分析仪和HE染色分别在ZDF大鼠中检测生化指标和肝组织病理学。进行肝组织的微阵列分析，并通过定量实时PCR（qPCR）和蛋白质印迹检查差异表达基因（DEG）的水平。此外，还在HepG2-IR细胞中研究了BBR的作用。葡萄糖氧化酶法和荧光葡萄糖类似物分别用于检测葡萄糖消耗和摄取。使用PKA抑制剂H89，ELISA，qPCR，Western印迹和免疫荧光染色来评估相关信号通路的表达水平。为了评估PPM1B的作用，用靶向PPM1B的慢病毒稳定感染了HepG2-IR细胞。使用BBR可以大大减轻体重，PPM1B上调的ZDF大鼠的尿量，血糖，血尿素氮（BUN），CHOL，肝指数水平以及病理变化和改善的ALB水平。此外，BBR可有效改善HepG2-IR细胞的葡萄糖消耗，摄取和炎症。PPM1B表达的敲低加剧了HepG2-IR细胞的炎症反应和糖代谢异常。从机理上讲，cAMP，PKA，PPM1B，PPAR的表达发生逆转γ，LRP1，GLUT4，NF- κ乙P65，JNK，PIKK β Ser181，IKK β，IRS-1 Ser307，IRS-1，IRS-2 Ser731，IRS-2，PI3K的p85和AKT Ser473上有助于改善IR中用BBR处理的HepG2-IR细胞。总之，这些结果表明，BBR可能通过环磷酸腺苷，PKA，PPM1B，PPAR调节调节IR进展γ，LRP11，GLUT4，NF- κ乙P65，JNK，PIKK β Ser181，IKK β，IRS-1 Ser307，IRS -1，IRS-2 Ser731，IRS-2，PI3K p85和AKT Ser473在肝脏中的表达。