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DPP-4 抑制剂联合槲皮素的口服制剂改善 1 型糖尿病大鼠的代谢稳态。

Oral formulation of DPP-4 inhibitor plus Quercetin improves metabolic homeostasis in type 1 diabetic rats.

机构信息

Laboratório de Bioquímica Metabólica (LBM), Departamento de Ciências Biológicas (DECBI), Universidade Federal de Ouro Preto (UFOP), Ouro Preto, MG, 35400-000, Brazil.

Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Ouro Preto (UFOP), Ouro Preto, MG, 35400-000, Brazil.

出版信息

Sci Rep. 2018 Oct 17;8(1):15310. doi: 10.1038/s41598-018-33727-x.

DOI:10.1038/s41598-018-33727-x
PMID:30333575
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6192983/
Abstract

This study aimed to investigate the potential of an oral formulation (QV formulation) containing Quercetin and a Dipeptidyl Peptidase-4 Inhibitor (DPP-4 inhibitor), Vildagliptin, in improving metabolic homeostasis in type 1 diabetes model. Female albino Fischer rats were divided into four groups: untreated control animals (C), untreated diabetic animals (D), diabetic animals treated with QV formulation (DQV), and diabetic animals treated with insulin (DI). Diabetes was induced by injection of alloxan (135 mg kg body mass) and confirmed by glycemic test. After the 30-day treatment period, biochemical parameters were analyzed in the pancreas, liver, and serum. Histopathological changes in pancreatic tissue were examined by Hematoxyline & Eosin staining and the insulin content in the islet measured by immunohistochemistry with anti-insulin antibody. The glycogen content in the hepatocytes was quantified by Periodic Schiff Acid staining. The QV formulation reduced the glycemia, preserved the pancreatic architecture, increased insulin levels, furthermore ameliorated lipid profile and to promote higher survival rate of animals. Together, our data suggest that the QV formulation treatment was able to normalize metabolic homeostasis in type 1 diabetic rats.

摘要

本研究旨在探讨含有槲皮素（Quercetin）和二肽基肽酶-4 抑制剂（DPP-4 抑制剂）维格列汀（Vildagliptin）的口服制剂（QV 制剂）改善 1 型糖尿病模型代谢稳态的潜力。将雌性白化 Fischer 大鼠分为四组：未治疗对照组（C）、未治疗糖尿病组（D）、糖尿病用 QV 制剂治疗组（DQV）和糖尿病用胰岛素治疗组（DI）。通过注射链脲佐菌素（135mg/kg 体重）诱导糖尿病，并通过血糖试验进行确认。在 30 天治疗期结束后，分析胰腺、肝脏和血清中的生化参数。通过苏木精和曙红染色检查胰腺组织的组织病理学变化，并通过抗胰岛素抗体的免疫组织化学法测量胰岛中的胰岛素含量。通过过碘酸希夫染色定量肝细胞中的糖原含量。QV 制剂降低了血糖，保持了胰腺结构，增加了胰岛素水平，此外改善了血脂谱并提高了动物的存活率。总之，我们的数据表明，QV 制剂治疗能够使 1 型糖尿病大鼠的代谢稳态正常化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/1fb8b0735a18/41598_2018_33727_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/f25519290fe8/41598_2018_33727_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/e141217703c4/41598_2018_33727_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/9999dca5fd14/41598_2018_33727_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/e681f3e4b702/41598_2018_33727_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/952ca8ff2f7e/41598_2018_33727_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/d76976c18c18/41598_2018_33727_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/d20d5daa8dfc/41598_2018_33727_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/1fb8b0735a18/41598_2018_33727_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/f25519290fe8/41598_2018_33727_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/e141217703c4/41598_2018_33727_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/9999dca5fd14/41598_2018_33727_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/e681f3e4b702/41598_2018_33727_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/952ca8ff2f7e/41598_2018_33727_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/d76976c18c18/41598_2018_33727_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/d20d5daa8dfc/41598_2018_33727_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/637f/6192983/1fb8b0735a18/41598_2018_33727_Fig8_HTML.jpg

相似文献

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Oral formulation of DPP-4 inhibitor plus Quercetin improves metabolic homeostasis in type 1 diabetic rats.

Sci Rep. 2018-10-17

[2]
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[3]
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J Diabetes Complications. 2012-5-22

[4]
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[5]
Chronic DPP-IV inhibition with PKF-275-055 attenuates inflammation and improves gene expressions responsible for insulin secretion in streptozotocin induced diabetic rats.

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[6]
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[7]
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[8]
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Biochem Pharmacol. 2011-10-12

[9]
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J Cardiovasc Pharmacol Ther. 2018-3

[10]
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J Clin Endocrinol Metab. 2011-1-14

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[3]
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本文引用的文献

[1]
Possible Long-Term Efficacy of Sitagliptin, a Dipeptidyl Peptidase-4 Inhibitor, for Slowly Progressive Type 1 Diabetes (SPIDDM) in the Stage of Non-Insulin-Dependency: An Open-Label Randomized Controlled Pilot Trial (SPAN-S).

Diabetes Ther. 2017-10

[2]
Effects of Vildagliptin Add-on Insulin Therapy on Nocturnal Glycemic Variations in Uncontrolled Type 2 Diabetes.

Diabetes Ther. 2017-10

[3]
Metformin Improves Endothelial Function and Reduces Blood Pressure in Diabetic Spontaneously Hypertensive Rats Independent from Glycemia Control: Comparison to Vildagliptin.

Sci Rep. 2017-9-8

[4]
Plasma matrix metalloproteinases are associated with incident cardiovascular disease and all-cause mortality in patients with type 1 diabetes: a 12-year follow-up study.

Cardiovasc Diabetol. 2017-4-26

[5]
Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy.

J Mol Endocrinol. 2017-7

[6]
A murine model of type 2 diabetes mellitus developed using a combination of high fat diet and multiple low doses of streptozotocin treatment mimics the metabolic characteristics of type 2 diabetes mellitus in humans.

J Pharmacol Toxicol Methods. 2017

[7]
The efficacy and safety of DPP4 inhibitors in patients with type 1 diabetes: A systematic review and meta-analysis.

Diabetes Res Clin Pract. 2016-11

[8]
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Zhongguo Zhong Yao Za Zhi. 2015-12

[9]
Non-insulin drugs to treat hyperglycaemia in type 1 diabetes mellitus.

Lancet Diabetes Endocrinol. 2016-3-9

[10]
Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism.

Diabetologia. 2016-5

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