Abstract：
AIMS AND BACKGROUND:Type 2 diabetes is a chronic disease that cannot be treated adequately using the known monotherapies, especially when the disease progresses to an advanced stage. In this study, we explore the possibility of treating the disease with a novel combination approach of oleanolic acid (OA), a glycogen phosphorylase (GP) inhibitor, and metformin. METHODS:Db/db mice were randomly divided into four groups: a db/db control group, db/db mice treated with OA (250 mg/kg), db/db mice treated with metformin (100 mg/kg), and db/db mice treated with a combination of OA and metformin. All mice were treated for four weeks. The effects of the treatments on glucose homeostasis were measured using an OGTT, an assessment of insulin sensitivity and signaling in the liver, and the hepatic glucose production. RESULTS:Combination therapy with OA and metformin significantly reduced the blood glucose and insulin levels and improved the liver pathology compared with that for the monotherapy in the db/db diabetic mouse model. We also found that the combination therapy significantly increased the mRNA expression of glycogen synthesis and decreased the GP, PGC-1α, PEPCK1, and G-6-Pase levels. In addition, the combination therapy with OA and metformin significantly increased the phosphorylation of AKT, PI3K, AMPK, and ACC and decreased the protein expression levels of G-6-Pase, PEPCK1, and TORC compared with those for either monotherapy. The combination therapy also reduced the phosphorylation of mTOR and CREB. CONCLUSIONS:Our results suggest that the combination therapy with OA and metformin has synergistic effects on the symptoms of db/db diabetic mice by improving glucose and insulin homeostasis.
journal_name
J Diabetes Resjournal_title
Journal of diabetes researchauthors
Wang X,Chen Y,Abdelkader D,Hassan W,Sun H,Liu Jdoi
10.1155/2015/973287subject
Has Abstractpub_date
2015-01-01 00:00:00pages
973287eissn
2314-6745issn
2314-6753journal_volume
2015pub_type
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
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journal_title：Journal of diabetes research
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journal_title：Journal of diabetes research
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
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更新日期：2018-10-03 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
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journal_title：Journal of diabetes research
pub_type： 杂志文章
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
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pub_type： 杂志文章
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
doi：10.1155/2015/908152
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2015/102054
更新日期：2015-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
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更新日期：2020-03-09 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2020/2132037
更新日期：2020-11-16 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
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更新日期：2019-06-02 00:00:00
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pub_type： 杂志文章,随机对照试验
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更新日期：2016-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2018/1390418
更新日期：2018-11-11 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
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更新日期：2016-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章
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pub_type： 杂志文章,meta分析
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更新日期：2019-09-05 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章,已发布勘误
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更新日期：2018-10-22 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2020/4742952
更新日期：2020-11-18 00:00:00
abstract：:Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signa...
journal_title：Journal of diabetes research
pub_type： 杂志文章,评审
doi：10.1155/2016/2868652
更新日期：2016-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2016/3159103
更新日期：2016-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2014/421827
更新日期：2014-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2014/107152
更新日期：2014-01-01 00:00:00
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journal_title：Journal of diabetes research
pub_type： 杂志文章
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更新日期：2016-01-01 00:00:00
abstract：:miR-122, the expression of which is regulated by several transcription factors, such as HNF1A, was recently reported to be associated with type 2 diabetes (T2DM) and hepatocellular carcinoma. HNF1A variants can cause diabetes and might be involved in the development of primary liver neoplasm. Differences in miR-122 ex...
journal_title：Journal of diabetes research
pub_type： 杂志文章
doi：10.1155/2018/7842064
更新日期：2018-08-01 00:00:00
