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基于Zucker糖尿病脂肪大鼠模型的维生素K2及其在2型糖尿病中的治疗潜力

Menaquinone-7 and its therapeutic potential in type 2 diabetes mellitus based on a Zucker diabetic fatty rat model.

作者信息

Mrosewski Ingo, Mantel Valeriya, Urbank Matthias, Schulze-Tanzil Gundula, Werner Christian, Gögele Clemens, Kokozidou Maria, Bertsch Thomas

机构信息

MDI Limbach Berlin GmbH, Aroser Allee 84, 13407, Berlin, Germany.

Berlin University of Applied Sciences and Technology, Luxemburger Str. 10, 13353, Berlin, Germany.

出版信息

Heliyon. 2024 Dec 3;10(23):e40826. doi: 10.1016/j.heliyon.2024.e40826. eCollection 2024 Dec 15.

DOI:10.1016/j.heliyon.2024.e40826
PMID:39719993
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11666950/
Abstract

BACKGROUND

Type 2 diabetes mellitus (T2DM) is marked by insulin resistance, low grade chronic inflammation, and endothelial dysfunction. Vitamin K2, especially menaquinone-7 (MK-7), might delay T2DM progression and alleviate its consequences. Hence, this study evaluated the effects of MK-7 on serum and urine markers of diabetes in an animal model of T2DM.

METHODS

Hetero- (fa/+, control) and homozygous (fa/fa, diabetic) male Zucker diabetic fatty (ZDF) rats were supplemented or not with MK-7 for 12 weeks. After euthanasia, vitamin K1, menaquinone-4 and MK-7 serum concentrations were analyzed via reversed phase high pressure liquid chromatography. Glucose (serum), fructosamine (serum) and creatinine (serum and urine) levels were assessed photometrically, serum cystatin C and urinary total protein were turbidimetrically determined. Serum transforming growth factor beta 1 (TGF-β1) and procollagen type III N-terminal peptide (PIIINP) were quantified with enzyme-linked immunosorbent assay. Urinary marker proteins were analyzed via sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Nephropathy was assessed histologically.

RESULTS

Supplementation led to significantly elevated MK-7 serum levels and a significant reduction of PIIINP serum levels in both hetero- and homozygous ZDF rats. Additionally, not statistically significant reductions of TGF-β1 serum levels, proteinuria as well as the nephropathy score were observed. body mass, serum fructosamine, glucose, cystatin C and creatinine levels were unaffected.

CONCLUSION

MK-7 reduced serum markers of fibrosis, histological features of nephropathy and urinary protein excretion, but failed to affect serum markers of T2DM. The therapeutic potential of MK-7 in T2DM and its mode of action should be further investigated in more detail.

摘要

背景

2型糖尿病（T2DM）的特征是胰岛素抵抗、低度慢性炎症和内皮功能障碍。维生素K2，尤其是甲萘醌-7（MK-7），可能会延缓T2DM的进展并减轻其后果。因此，本研究在T2DM动物模型中评估了MK-7对糖尿病血清和尿液标志物的影响。

方法

对杂合子（fa/+，对照）和纯合子（fa/fa，糖尿病）雄性Zucker糖尿病脂肪大鼠（ZDF）补充或不补充MK-7，持续12周。安乐死后，通过反相高压液相色谱法分析维生素K1、甲萘醌-4和MK-7的血清浓度。通过比色法评估葡萄糖（血清）、果糖胺（血清）和肌酐（血清和尿液）水平，通过比浊法测定血清胱抑素C和尿总蛋白。采用酶联免疫吸附测定法定量血清转化生长因子β1（TGF-β1）和III型前胶原N端肽（PIIINP）。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析尿液标志物蛋白。通过组织学评估肾病。

结果

补充MK-7导致杂合子和纯合子ZDF大鼠的MK-7血清水平显著升高，PIIINP血清水平显著降低。此外，观察到TGF-β1血清水平、蛋白尿以及肾病评分有非统计学意义的降低。体重、血清果糖胺、葡萄糖、胱抑素C和肌酐水平未受影响。

结论

MK-7降低了纤维化的血清标志物、肾病的组织学特征和尿蛋白排泄，但未能影响T2DM的血清标志物。MK-7在T2DM中的治疗潜力及其作用方式应进一步详细研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/6464f5650624/mmcfigs2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/84c540419155/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/cec9cbb0580d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/f6d1af7a59fd/gr2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/99df3dab7430/gr4.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/0a3e03b38629/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/9836a36d0bce/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/9215b51e3503/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/e3ea7a295094/gr9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/7154308de4bf/mmcfigs1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad11/11666950/6464f5650624/mmcfigs2.jpg

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