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他汀类药物可加重高蔗糖喂养的啮齿动物模型的葡萄糖不耐受和高血糖。

Statins exacerbate glucose intolerance and hyperglycemia in a high sucrose fed rodent model.

机构信息

Institute of Science, Nirma University, Ahmedabad, India.

Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Hyderabad, 500 046, India.

出版信息

Sci Rep. 2019 Jun 19;9(1):8825. doi: 10.1038/s41598-019-45369-8.

Abstract

Statins are first-line therapy drugs for cholesterol lowering. While they are highly effective at lowering cholesterol, they have propensity to induce hyperglycemia in patients. Only limited studies have been reported which studied the impact of statins on (a) whether they can worsen glucose tolerance in a high sucrose fed animal model and (b) if so, what could be the molecular mechanism. We designed studies using high sucrose fed animals to explore the above questions. The high sucrose fed animals were treated with atorvastatin and simvastatin, the two most prescribed statins. We examined the effects of statins on hyperglycemia, glucose tolerance, fatty acid accumulation and insulin signaling. We found that chronic treatment with atorvastatin made the animals hyperglycemic and glucose intolerant in comparison with diet alone. Treatment with both statins lead to fatty acid accumulation and inhibition of insulin signaling in the muscle tissue at multiple points in the pathway.

摘要

他汀类药物是降低胆固醇的一线治疗药物。虽然它们在降低胆固醇方面非常有效,但它们有使患者发生高血糖的倾向。只有有限的研究报道了他汀类药物对以下方面的影响:(a) 它们是否会在高蔗糖喂养的动物模型中使葡萄糖耐量恶化,以及 (b) 如果是这样,其分子机制是什么。我们使用高蔗糖喂养的动物设计了研究来探索上述问题。高蔗糖喂养的动物接受阿托伐他汀和辛伐他汀治疗,这两种是最常开的他汀类药物。我们检查了他汀类药物对高血糖、葡萄糖耐量、脂肪酸积累和胰岛素信号的影响。我们发现,与单独饮食相比,阿托伐他汀的慢性治疗使动物出现高血糖和葡萄糖不耐受。两种他汀类药物的治疗都导致脂肪酸在肌肉组织中的积累,并在通路的多个点抑制胰岛素信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/72f1/6584635/784bf6f692f0/41598_2019_45369_Fig1_HTML.jpg

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