Disorders of glucose metabolism and impaired energy metabolism in pfkma and pfkmb knockout zebrafish

IF 1.7 3区医学 Q3 ENDOCRINOLOGY & METABOLISM

General and comparative endocrinology Pub Date : 2025-07-23 DOI:10.1016/j.ygcen.2025.114787

Na Liu , Mengjie Li , Tianci Liu , Jitu Wang , Bo Zhang , Man Zhang

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引用次数: 0

Abstract

Background

In our previous study, Phosphofructokinase, muscle (PFKM), a key enzyme in glucose metabolism, was found to be decreased in the urinary exosomes of diabetic patients. The role of PFKM in glucose and energy metabolism is not fully understood. The study explores PFKM’s implications in these metabolic pathways through the lens of a zebrafish model.

Methods

We analyzed pfkma and pfkmb expressions in early zebrafish development using Daniocell and ZESTA databases and performed whole-mount in situ hybridization on embryos up to 4 days post-fertilization (dpf). The CRISPR/Cas9 system was utilized to generate pfkma and pfkmb knockout zebrafish, and the expression of various genes, including β-actin, pfkma, pfkmb, peo1, mfn1, drp1, nd2, cytb, cox3, and atp6, was measured by qRT-PCR in the embryos.

Results

Knockout mutants displayed elevated glucose levels across whole embryos. Additionally, at 5 dpf, pfkma and pfkmb double mutants showed pancreatic islet proliferation, ATP depletion, downregulation of the expression of the mitochondrial-related gene peo1, and impaired locomotor activity.

Conclusions

PFKM plays an important role in stabilizing glucose metabolism and has a certain impact on mitochondrial energy metabolism pathways in zebrafish model.

查看原文本刊更多论文

pfkma和pfkmb敲除对斑马鱼糖代谢紊乱和能量代谢的影响。

背景：在我们之前的研究中，发现糖尿病患者尿外泌体中葡萄糖代谢的关键酶磷酸果糖激酶（PFKM）减少。PFKM在葡萄糖和能量代谢中的作用尚不完全清楚。该研究通过斑马鱼模型探讨了PFKM在这些代谢途径中的影响。方法：利用Daniocell和ZESTA数据库分析pfkma和pfkmb在斑马鱼早期发育过程中的表达，并对4天大的胚胎进行全载原位杂交。利用CRISPR/Cas9系统构建pfkma和pfkmb敲除斑马鱼，qRT-PCR检测胚胎中β-actin、pfkma、pfkmb、peo1、mfn1、drp1、nd2、cytb、cox3和atp6等多种基因的表达。结果：敲除突变体在整个胚胎中显示葡萄糖水平升高。此外，在受精后5 天（dpf）， pfkma和pfkmb双突变体表现出胰岛增生，ATP水平下降，线粒体相关基因peo1表达减少，运动活性降低。结论：PFKM在稳定斑马鱼模型葡萄糖代谢中具有重要作用，并对线粒体能量代谢途径有一定影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

General and comparative endocrinology 医学-内分泌学与代谢

CiteScore

5.60

自引率

7.40%

发文量

120

审稿时长

2 months

期刊介绍： General and Comparative Endocrinology publishes articles concerned with the many complexities of vertebrate and invertebrate endocrine systems at the sub-molecular, molecular, cellular and organismal levels of analysis.