Berberine inhibits glucose oxidation and insulin secretion in rat islets
Berberine inhibits glucose oxidation and insulin secretion in rat islets
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小檗碱抑制大鼠胰岛葡萄糖氧化和胰岛素分泌
DOI：
10.1507/endocrj.ej17-0543
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发表时间：
2018-01-01
影响因子：
2
通讯作者：
Zhou, Libin
中科院分区：
文献类型：
--
作者：
Bai, Mengyao;Liu, Yun;Zhou, Libin
葡萄糖主要通过其代谢和β细胞中代谢耦合因子的产生来促进胰岛素分泌。 AMP激活蛋白激酶（AMPK）的激活（一种能量传感器）导致β细胞的胰岛素分泌减少，但其机制仍然很少知道。 Berberine是一种口服抗糖尿病药物，已显示可激活多种外围组织中的AMPK。在这里，我们检查了小鼠胰岛中少碱和AMPK激活对胰岛素分泌和葡萄糖氧化的影响。我们的结果表明，小berine抑制了具有AMPK激活的大鼠胰岛的葡萄糖刺激的胰岛素分泌。当葡萄糖浓度升高到25 mmol/L时，berberine对胰岛素分泌的抑制作用消失了。此外，大鼠胰岛中高葡萄糖诱导的氧气消耗率（OCR）和ATP产生显着降低。尽管腺病毒介导的组成激活AMPK的过表达显着降低了大鼠胰岛的GSI和OCR，但化合物C对AMPK的抑制并未逆转berberine抑制的OCR。此外，小ber虫减弱了脂肪酸合酶的葡萄糖刺激的表达。这些结果表明，小berine介导的葡萄糖氧化减速与独立于AMPK激活的胰岛分泌减少紧密联系，并且抑制脂肪酸合成也可能有助于berberine对胰岛素分泌的作用。
Glucose promotes insulin secretion primarily via its metabolism and the production of metabolic coupling factors in beta-cells. The activation of AMP-activated protein kinase (AMPK), an energy sensor, results in a decrease in insulin secretion from beta-cells, but its mechanism remains largely unknown. Berberine, an oral anti-diabetic drug, has been shown to activate AMPK in multiple peripheral tissues. Here, we examined the effects of berberine and AMPK activation on insulin secretion and glucose oxidation in rat islets. Our results showed that berberine inhibited glucose-stimulated insulin secretion from rat islets with AMPK activation. When glucose concentration was elevated to 25 mmol/L, the inhibitory action of berberine on insulin secretion disappeared. Furthermore, berberine significantly decreased oxygen consumption rate (OCR) and ATP production induced by high glucose in rat islets. Although adenovirus-mediated overexpression of constituent-activated AMPK markedly decreased GSIS and OCR in rat islets, the inhibition of AMPK by compound C did not reverse berberine-suppressed OCR. In addition, berberine attenuated glucose-stimulated expression of fatty acid synthase. These results indicate that berberine-mediated deceleration of glucose oxidation is tightly link to the decreased insulin secretion in islets independent of AMPK activation and inhibition of fatty acid synthesis may also contribute to the effect of berberine on insulin secretion.