Abstract Context: Berberine is an alkaloid that possesses various pharmacologic effects. Objective: To explore the mechanism of berberine to improve insulin sensitivity in fructose-fed mice. Materials and methods: Sixty male ICR mice were randomly divided into 6 groups (10 mice in each group): control, fructose, pioglitazone (10 mg/kg) and berberine (50, 100, and 200 mg/kg). Except for the control group, the mice received 20% fructose drinking for 10 weeks. Pioglitazone and berberine were orally administered once daily during the last 4 weeks. The insulin sensitivity was evaluated using an oral glucose tolerance test (OGTT). The serum levels of fasting glucose and insulin, blood lipids, and hormones were determined. The hepatic AMP and ATP contents were detected using high performance liquid chromatography (HPLC) analysis, and the protein expression was examined by immunoblotting. Results: Berberine significantly reversed the insulin resistance induced by fructose, including lowering fasting insulin levels (from 113.9 to 67.4) and area under the curve (AUC) during OGTT (from 1310 to 1073), decreasing serum leptin (from 0.28 to 0.13) and increasing serum adiponectin levels (from 1.50 to 2.80). Moreover, berberine enhanced the phosphorylation levels of protein kinase B (PKB/AKT; 2.27-fold) and glycogen synthase kinase-3β (GSK3β; 2.56-fold), and increased hepatic glycogen content (from 0.19 to 1.65). Furthermore, berberine upregulated the protein expression of peroxisome proliferator activated receptor gamma coactivator 1α (PGC1α; 2.61-fold), phospho-AMP-activated protein kinase (p-AMPK; 1.35-fold) and phospho-liver kinase B1 (p-LKB1; 1.41-fold), whereas it decreased the AMP/ATP ratio (from 4.25 to 1.82). Conclusion: The present study demonstrated the protective effects of berberine against insulin resistance induced by fructose. Our findings may provide an experimental basis for the application of berberine in the treatment of insulin resistance.

中文翻译：

---

小檗碱通过刺激小鼠肝脏 LKB1/AMPK/PGC1α 通路减弱果糖诱导的胰岛素抵抗

摘要背景：小檗碱是一种具有多种药理作用的生物碱。目的：探讨小檗碱改善果糖喂养小鼠胰岛素敏感性的机制。材料和方法：60 只雄性 ICR 小鼠随机分为 6 组（每组 10 只小鼠）：对照组、果糖、吡格列酮（10 mg/kg）和小檗碱（50、100 和 200 mg/kg）。除对照组外，小鼠接受 20% 果糖饮用 10 周。在过去 4 周内每天口服一次吡格列酮和小檗碱。使用口服葡萄糖耐量试验（OGTT）评估胰岛素敏感性。测定空腹血糖和胰岛素、血脂和激素的血清水平。使用高效液相色谱 (HPLC) 分析检测肝 AMP 和 ATP 含量，并通过免疫印迹检查蛋白质表达。结果：小檗碱显着逆转果糖诱导的胰岛素抵抗，包括降低空腹胰岛素水平（从 113.9 到 67.4）和 OGTT 期间的曲线下面积（AUC）（从 1310 到 1073），降低血清瘦素（从 0.28 到 0.13）和增加血清脂联素水平（从 1.50 到 2.80）。此外，小檗碱增强了蛋白激酶 B（PKB/AKT；2.27 倍）和糖原合酶激酶 3β（GSK3β；2.56 倍）的磷酸化水平，并增加了肝糖原含量（从 0.19 到 1.65）。此外，小檗碱上调过氧化物酶体增殖物激活受体 γ 共激活因子 1α（PGC1α；2.61 倍）、磷酸化 AMP 激活蛋白激酶（p-AMPK；1.35 倍）和磷酸化肝激酶 B1（p-LKB1； 1.41 倍），而它降低了 AMP/ATP 比率（从 4.25 到 1.82）。结论：本研究证明了小檗碱对果糖诱导的胰岛素抵抗的保护作用。我们的研究结果可能为小檗碱在胰岛素抵抗治疗中的应用提供实验依据。