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Uncoupling protein‐2 mediates the protective action of berberine against oxidative stress in rat insulinoma INS ‐1 E cells and in diabetic mouse islets
Author(s) -
Liu Limei,
Liu Jian,
Gao Yuansheng,
Yu Xiaoxing,
Xu Gang,
Huang Yu
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12666
Subject(s) - berberine , ampk , insulin , endocrinology , oxidative stress , medicine , nitrotyrosine , chemistry , pancreatic islets , biology , phosphorylation , islet , protein kinase a , biochemistry , nitric oxide synthase , nitric oxide
Background and Purpose Uncoupling protein‐2 ( UCP 2) may regulate glucose‐stimulated insulin secretion. The current study investigated the effects of berberine, an alkaloid found in many medicinal plants, on oxidative stress and insulin secretion through restoration of UCP 2 expression in high glucose ( HG )‐treated INS ‐1 E cells and rat islets or in db/db mouse islets. Experimental Approach Mouse and rat pancreatic islets were isolated. Nitrotyrosine, superoxide dismutase ( SOD )‐1 and UCP 2 expression and AMPK phosphorylation were examined by Western blotting. Insulin secretion was measured by elisa . Mitochondrial reactive oxygen species ( ROS ) production was detected by confocal microscopy. Key Results Incubation of INS ‐1 E cells and rat islets with HG (30 mmol·L −1 ; 8 h) elevated nitrotyrosine level, reduced SOD ‐1 and UCP 2 expression and AMPK phosphorylation, and inhibited glucose‐stimulated insulin secretion. HG also increased mitochondrial ROS in INS ‐1 E cells. Co‐treatment with berberine inhibited such effects. The AMPK inhibitor compound C , the UCP 2 inhibitor genipin and adenovirus ucp2 sh RNA inhibited these protective effects of berberine. Furthermore, compound C normalized berberine‐stimulated UCP 2 expression but genipin did not affect AMPK phosphorylation. Islets from db/db mice exhibited elevated nitrotyrosine levels, reduced expression of SOD ‐1 and UCP 2 and AMPK phosphorylation, and decreased insulin secretion compared with those from db/m + mice. Berberine also improved these defects in diabetic islets and genipin blocked the effects of berberine. Conclusions and Implications Berberine inhibited oxidative stress and restored insulin secretion in HG ‐treated INS‐IE cells and diabetic mouse islets by activating AMPK and UCP 2. UCP 2 is an important signalling molecule in mediating anti‐diabetic effects of berberine.