Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Zhang, Jie; Qiu, Hongmei; Huang, Jiajun; Ding, Shumei; Huang, Bo; Wu, Qin; Jiang, Qingsong

doi:10.1111/iep.12296

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…After 12 weeks of modelling, we found that LVIDd and LVIDs of the ventricular wall structure were increased, and LVEF and LVFS of systolic cardiac function were significantly decreased, indicating abnormal cardiac function and successful modelling. These results were consistent with the modelling reported previously [ 16 , 17 ] . In addition, immunohistochemical staining showed that the myocardial fibres of the rats in the model group were damaged and broken, and many small necrotic foci were visible.…”

Section: Discussionsupporting

confidence: 94%

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca 2+ overload and the TGF-β1/Smad signaling pathway

Rong¹,

Zhou²,

Guo³

et al. 2023

ABBS

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The inwardly rectifying potassium channel Kir2.1 is closely associated with many cardiovascular diseases. However, the effect and mechanism of Kir2.1 in diabetic cardiomyopathy remain unclear. In vivo , we use STZ to establish the model, and ventricular structural changes, myocardial inflammatory infiltration, and myocardial fibrosis severity are detected by echocardiography, histological staining, immunohistochemistry, and western blot analysis, respectively. In vitro , a myocardial fibrosis model is established with high glucose. The Kir2.1 current amplitude, intracellular calcium concentration, fibrosis-related proteins, and TGF-β1/Smad pathway proteins are detected by whole-cell patch clamp, calcium probes, western blot analysis, and immunofluorescence, respectively. The in vivo results show that compared to diabetic cardiomyopathy, zacopride (a Kir2.1 selective agonist) significantly reduces the left ventricular systolic diameter and diastolic diameter, increases the left ventricular ejection fraction and left ventricular short-axis shortening, improves the degree of cell necrosis, and reduces the expression of myocardial interstitial fibrosis protein and collagen fibre deposition area. The in vitro results show that the current amplitude and protein expression of Kir2.1 are both decreased in the high glucose-induced myocardial fibrosis model. Additionally, zacopride significantly upregulates the expression of Kir2.1 and inhibits the expressions of the fibrosis-related proteins α-SMA, collagen I, and collagen III. Activation of Kir2.1 reduces the intracellular calcium concentration and inhibits the protein expressions of TGF-β1 and p-Smad 2/3. Activation of Kir2.1 can improve myocardial fibrosis induced by diabetic cardiomyopathy, and the possible mechanism may be related to inhibiting Ca 2+ overload and the TGF-β1/Smad signaling pathway.

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Section: Discussionsupporting

confidence: 94%

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca 2+ overload and the TGF-β1/Smad signaling pathway

Rong¹,

Zhou²,

Guo³

et al. 2023

ABBS

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“…The current study found strong support for an association between HOMA-IR and diabetic cardiomyopathy [18], and that insulin resistance is associated with diastolic dysfunction and the risk of heart failure [19].…”

Section: 1gck Knockout Induced Metabolic Disturbances and Cardiac Dsupporting

confidence: 62%

Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

Li¹,

Xu²,

Mao³

et al. 2020

Preprint

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Background: Diabetic cardiomyopathy is a ventricular disease caused by diabetes mellitus. Abnormalities in the function of the glucokinase (GCK) play an important role in the development of diabetes. The present study is aimed at exploring changes in gene expression and related molecular mechanisms of diabetic myocardial injury in Gck knockout mice. Methods: Liver-specific glucokinase gene knockout mice( Gck w/- ) and wide type ( Gck w/w )mice generated using the Cre-loxP gene targeting strategy of 30- and 60-weeks of age were used in these studies. Determination of liver glucokinase enzyme activity, liver glycogen content and serum biochemistry parameters reflect the metabolic disorder in these mice. Echocardiography and surface electrocardiographs were used to evaluate cardiac function. Superoxide dismutase activity and malondialdehyde levels reflect oxidative stress in the myocardium. RNAseq, GO enrichment analysis and qPCR wereused to detect differences in the myocardial gene expression profiles of Gck w/- and Gck w/w mice. Results: Hyperglycemia and insulin resistance induced by decreased liver glucokinase expression and enzyme activity throughout the life of heterozygous Gck knockout mice do not yield body weight significant difference. However, prolonged PR interval and QRS duration, decreased left ventricular diameter and increased thickness of the posterior wall of the left ventricle were accompanied by increase of PAS and Masson positive substances in the myocardium of 60-week-old Gck knockout mice. RNAseq analysis showed that genes related tothe myosin heavy and light chains, insulin signaling pathway and oxidative phosphorylation were significantly differentially expressedbetween60-week-old Gck w/- and Gck w/w mice. Phosphorylation of AMPKβ1 and ACC in 60-week-old Gck knockout mice was decreased. Conclusions: Liver-specific Gck knock-out can induce myocardial fibrosis at an early stage and diabetic myocardial injury at alate stage. Through this process, the proportion of myosin heavy chain and light chain falls out of balance, the insulin signal pathway becomes down regulated and mitochondrial oxidative stress is up regulated, leading to myocardial disease.

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“…On the third day after STZ injection (the last day of week 6), the blood glucose levels of the mice were measured. The successful establishment of the DM model was confirmed by fasting plasma glucose levels of >11.1 mmol/l and postprandial plasma glucose levels of >16.7 mmol/l (16,17).…”

Section: Animals and Animal Groups A Total Of 24 Malementioning

confidence: 89%

lncRNA uc.48+ regulates immune and inflammatory reactions mediated by the P2X7 receptor in type 2 diabetic mice

Jiang

Liu

et al. 2020

Exp Ther Med

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Diabetes and non-coding RNAs are receiving increasing attention in contemporary medical research. The present study aimed to explore the role of the long non-coding RNA uc.48+ in the pathological changes of type 2 diabetes mellitus (T2DM) by observing the effects of uc.48+ small interfering RNA (siRNA) on the abdominal cells of a mouse model of T2DM. Mice with T2DM (DM group) were established by feeding with a high-sugar and-fat diet combined with intraperitoneal injections of low-dose streptozotocin. An intraperitoneal injection of uc.48+ siRNA was administered to the diabetic mice, and the serum levels of cytokines together with other clinical parameters, namely blood pressure, heart rate, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were examined. Following the collection and identification of abdominal cells from the mice, the mRNA levels of uc.48+, mRNA and protein levels of the P2X 7 receptor, and phosphorylation levels of ERK1/2 were evaluated by reverse transcription-PCR and western blotting, respectively. The MWT and TWL were significantly decreased in the DM group compared with the non-diabetic control group. However, the reductions in MWT and TWL were significantly attenuated following uc.48+ siRNA injection. The systolic and diastolic blood pressure, as well as the serum levels of tumor necrosis factor α and interleukin 1β of mice in the DM group were significantly increased compared with those in the control group, whereas these changes were significantly attenuated following the injection of uc.48+ siRNA. In addition, the expression levels of P2X 7 receptor mRNA and protein, and the degree of phosphorylation of ERK1/2 in the abdominal cells were significantly increased in the DM group compared with the control group. These changes were also significantly attenuated following transfection with uc.48+ siRNA in vivo. In conclusion, these data suggest that uc.48+ may play an important role in the pathological changes of blood pressure, neurology and abdominal cell function in T2DM via interaction with the P2X 7 receptor.

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Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Cited by 10 publications

References 20 publications

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca <sup>2+</sup> overload and the TGF-β1/Smad signaling pathway

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca <sup>2+</sup> overload and the TGF-β1/Smad signaling pathway

Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

lncRNA uc.48+ regulates immune and inflammatory reactions mediated by the P2X7 receptor in type 2 diabetic mice

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Establishment of a diabetic myocardial hypertrophy model in Mus musculus castaneus mouse

Cited by 10 publications

References 20 publications

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca &lt;sup&gt;2+&lt;/sup&gt; overload and the TGF-&beta;1/Smad signaling pathway

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca &lt;sup&gt;2+&lt;/sup&gt; overload and the TGF-&beta;1/Smad signaling pathway

Identification of Differentially Expressed Genes and Processes in Myocardial Tissue of Liver-Specific Gck Knockout Mice

lncRNA uc.48+ regulates immune and inflammatory reactions mediated by the P2X7 receptor in type 2 diabetic mice

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Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca <sup>2+</sup> overload and the TGF-β1/Smad signaling pathway

Activation of Kir2.1 improves myocardial fibrosis by inhibiting Ca <sup>2+</sup> overload and the TGF-β1/Smad signaling pathway