Endogenous L‐Carnosine Level in Diabetes Rat Cardiac Muscle

Liu, Yali; Su, Dan; Zhang, Ling; Wei, Shaofeng; Liu, Kuangyi; Mi, Peng; Li, Hanyun; Song, Yonggui

doi:10.1155/2016/6230825

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…Carnosine is a histidine-containing dipeptide anti-oxidant that serves as a major endogenous quencher of RCS via intramolecular Michael addition 17 and is therefore a promising candidate as a therapeutic agent. This could potentially offer particularly high levels of protection in T2D, as significantly decreased levels of carnosine have been found in the kidneys 18 and cardiac muscle 19 in mouse models of diabetes, and in human skeletal muscle of type 2 diabetes patients 20 . Some of these findings are however controversial, and future studies might therefore seek to generate carnosine synthase (CARNS1−/−) knockout animals to provide a tissue carnosine depleted model, carnosinase-1 (CNDP1−/−) knockout animals to provide a plasma carnosine full model, and carnosinase-2 (CNDP2−/−) knockout animals to provide a tissue carnosine full model.…”

Section: Discussionmentioning

confidence: 99%

Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

Cripps

Hanna

Lavilla

et al. 2017

Sci Rep

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The worldwide prevalence of diabetes has risen to 8.5% among adults, which represents a staggering rise in prevalence from 4.7% in 1980. Whilst some treatments work by increasing insulin secretion, over time their effectiveness decreases. We aim to increase insulin secretion by developing strategies that work through mechanisms independent of current treatment options. Isolated CD1 mouse islets, INS-1 pancreatic β-cells, or C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. Intracellular reactive species content was assayed using 2′,7′-dichlorofluorescein diacetate dye, inducible nitric oxide synthase levels determined by Western blot, 3-nitrotyrosine and 4-hydrpxnonenal both assayed by ELISA, insulin secretion quantified using ELISA or radioimmunoassay, and glucose uptake determined through 2-deoxy glucose 6 phosphate luminescence. Our data indicate that carnosine, a histidine containing dipeptide available through the diet, is an effective scavenger of each of the aforementioned reactive species. This results in doubling of insulin secretion from isolated mouse islets or INS-1 β-cells. Crucially, carnosine also reverses glucolipotoxic inhibition of insulin secretion and enhances glucose uptake into skeletal muscle cells. Thus, carnosine, or non-hydrolysable carnosine analogs, may represent a new class of therapeutic agent to fight type 2 diabetes.

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Section: Discussionmentioning

confidence: 99%

Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

Cripps

Hanna

Lavilla

et al. 2017

Sci Rep

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“…Liu Y, etc. using HPLC-UV a novel method for quantitation of cardiac muscle carnosine levels, the concentration of carnosine was significantly lower in the diabetes rats group, compared to that in the healthy control rats [16] . Nevertheless, what about human serum carnosine levels in diabetes mellitus and diabetic cardiomyopathy?…”

Section: Discussionmentioning

confidence: 93%

Analysis of Endogenous Antioxidant Peptides and Oxidative Stress Levels in Diabetic Cardiomyopathy

Qi¹,

Chang²,

Wu³

et al. 2018

dtbh

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Abstract. To investigate endogenous carnosine, glutathione system and oxidative stress levels in serum of patients with diabetic cardiomyopathy, and analyze relationships among endogenous carnosine, glutathione system and oxidative stress of patients with diabetic cardiomyopathy. The serum of 68 healthy people (NC), 75 patients with type 2 diabetes mellitus (DM) and 57 patients with diabetic cardiomyopathy (DCM) of the third affiliated hospital of QiQihar Medical University were collected. Carnosine content was measured by ELISA. T-GSH, GSH and GSSG were measured by micro-enzyme labeling. Clinical datas were compared: In comparison to NC group, BMI, FPG, 2hPG,C peptide and HbA1c in the DCM group and DM group increased significantly (P<0.05). The average value of human serum carnosine content, GSH content, GSH/GSSG ratio in the DM and DCM group were significantly lower than that in the control one (P<0.05). Serum endogenous antioxidant peptides and reduced glutathione (GSH) level drop and the imbalance of redox state in diabetic cardiomyopathy patients, which promote the occurrence and development of diabetic cardiomyopathy.

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“…The process of searching for potential biomarkers and pathways was as follows: (1) The differential metabolites between the Control and Model groups were de ned as arachidonic acid, eicosapentaenoic acid, linoleic acid and stearic acid, and the associated pathways were from the biosynthesis of unsaturated fatty acids, free fatty acid receptors, α-linolenic acid, linoleic acid metabolism, and the circadian clock (Supplementary Table 5 in Supplementary Information). (2) According to the comparison between the Model and RC groups, in addition to the differential metabolites identi ed between the Control and Model, branched chain amino acids (norvaline, L-alloisoleucine), betaine and 5-aminopentanoic acid were also found to be differential metabolites between the Model and RC groups (Supplementary Table 6 in Supplementary Information). (3) To further compare the differences among the three groups, we used the Bartlett test of homogeneity of variances in combination with a oneway ANOVA to estimate the p-values, as shown in Fig.…”

Section: Lc-ms Analysis Of the Serum Metabolic Pro Les And Candidate mentioning

confidence: 99%

Differential genes and microbiota revealed by serum metabolomics of obese rats after intervention by Rhizoma Coptidis

Zeng

Luo

et al. 2020

Preprint

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Background Integrating systems biology is an approach for investigating metabolic diseases in humans. However, few studies use this approach to investigate the mechanism by which Rhizoma Coptidis (RC) reduces the effect of glucose on high-fat induced obesity in rats. Methods Twenty-four specific pathogen-free (SPF) male Sprague-Dawley rats (80 ± 10 g) were used in this study. Serum metabolomics were detected by ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry. Liver tissue and cecum feces were used for RNA-Seq technology and 16S rRNA gene sequencing, respectively. Results We identified nine potential biomarkers, which are differential metabolites in the Control, Model and RC groups, including linoleic acid, eicosapentaenoic acid, arachidonic acid, stearic acid, and L-Alloisoleucine (p < 0.01). The liver tissue gene expression profile indicated the circadian rhythm pathway was significantly affected by RC (Q ≤ 0.05). A total of 149 and 39 operational taxonomic units (OTUs), which were highly associated with biochemical indicators and potential biomarkers in the cecum samples (FDR ≤ 0.05), respectively, were identified. Conclusions This work provides information to better understand the mechanism of the effect of RC intervention on the hypoglycemic effect in obese rats. The present study demonstrates that integrating systems biology may be a powerful tool to reveal the complexity of metabolic diseases in rats intervened by traditional Chinese medicine.

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Endogenous L‐Carnosine Level in Diabetes Rat Cardiac Muscle

Cited by 8 publications

References 23 publications

Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

Carnosine scavenging of glucolipotoxic free radicals enhances insulin secretion and glucose uptake

Analysis of Endogenous Antioxidant Peptides and Oxidative Stress Levels in Diabetic Cardiomyopathy

Differential genes and microbiota revealed by serum metabolomics of obese rats after intervention by Rhizoma Coptidis

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