Fructose induces mitochondrial dysfunction and triggers apoptosis in skeletal muscle cells by provoking oxidative stress

Abstract Mitochondrial dysfunction in skeletal muscle has been implicated in the development of insulin resistance, a major characteristic of type 2 diabetes. There is evidence that oxidative stress results from the increased production of reactive oxygen species and reactive nitrogen species leads to mitochondrial dysfunction, tissue damage, insulin resistance, and other complications observed in type 2 diabetes. It has been suggested that intake of high fructose contributes to insulin resistance and other metabolic disturbances. However, there is limited information about the direct effect of fructose on the mitochondrial function of skeletal muscle, the major metabolic determinant of whole body insulin activity. Here, we assessed the effect of fructose exposure on mitochondria-mediated mechanisms in skeletal muscle cells. Exposure of L6 myotubes to high fructose stimulated the production of mitochondrial reactive oxygen species and nitric oxide (NO), and the expression of inducible NO synthase. Fructose-induced oxidative stress was associated with increased translocation of nuclear factor erythroid 2-related factor-2 to the nucleus, decreases in mitochondrial DNA content and mitochondrial dysfunctions, as evidenced by decreased activities of citrate synthase and mitochondrial dehydrogenases, loss of mitochondrial membrane potential, decreased activity of the mitochondrial respiratory complexes, and impaired mitochondrial energy metabolism. Furthermore, positi...
Source: Apoptosis - Category: Molecular Biology Source Type: research

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In this study we further explore the therapeutic effect of PSTi8 on glucose metabolism in skeletal muscle cells/tissue and its effect on energy homeostasis in diet induced diabetic mice model. In in-vitro studies, we found that PSTi8 increases glucose uptake via enhanced GLUT4 translocation in L6 cells. This positive effect of PSTi8 led us to proceed with in-vivo studies in diabetic mice. C57BL/6 mice were fed HFD or HFrD diet for 12 weeks along with single STZ induction at 4th week followed by PSTi8 treatment. We found that HFD and HFrD model showed increased fat mass, caused glucose intolerance and insulin resistance, wi...
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research
Conclusions/interpretationTogether, these results demonstrate, in a unique human in vivo model, that a low mitochondrial oxidative capacity due to physical inactivity directly impacts IMCL accumulation and PKC θ translocation, resulting in impaired insulin signalling upon lipid infusion. This demonstrates the importance of mitochondrial oxidative capacity and muscle fat accumulation in the development of insulin resistance in humans.Trial registrationClinicalTrial.gov NCT01576250.FundingPS was supported by a ‘VICI’ Research Grant for innovative research from the Netherlands Organization for Scientific Res...
Source: Diabetologia - Category: Endocrinology Source Type: research
Abstract It was reported that either orexigenic neuropeptide galanin or anorexigenic hormone leptin caught benefit insulin sensitivity through increasing the translocation of glucose transporter 4 (GLUT4) in patients with diabetes. To date, it is unknown whether galanin can potentiate the effect of leptin on alleviation of insulin resistance. Therefore, in the current study we sought to assess the combined effect of central leptin and galanin on insulin resistance in the adipose tissues of type 2 diabetic rats. Galanin and leptin were injected into the intracerebroventricle of the diabetic rats, respectively, or c...
Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
In conclusion, the protective effect of HDL to counter ER stress and β-cell death involves the transport, generation, and mobilization of oxysterols for activation of the Hh signaling receptor SMO
Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Research Articles Source Type: research
Alogliptin inhibits IL-1β-induced inflammatory response in fibroblast-like synoviocytes. Int Immunopharmacol. 2020 Mar 14;83:106372 Authors: Guo Q, Zhang S, Huang J, Liu K Abstract Excessive production of pro-inflammatory cytokines such as interleukin (IL)-1β plays an important role in the chronic inflammation in fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). Alogliptin, an important selective dipeptidyl peptidase-4 (DPP-4) inhibitor licensed for the treatment of type 2 diabetes, has displayed a wide range of pharmacological capacities. In the present study, we aimed to inv...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. WEE was characterized by UPLC analysis. PA-treated HepG2 cells were selected as the IR cell model. The cell viability was determined using MTT assay. Moreover, the glucose consumption and production were measured by glucose oxidase method. The glucose uptake and glycogen content were determined by the 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose) glucose uptake assay and anthrone-sulfuric acid assay, respectively. The intracellular triglyceride conte...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract Lacking sunlight exposure, northern latitudes, and dietary vitamin D insufficiency are co-prevalent with metabolic syndrome (MetS), type-2 diabetes (T2D), and non-alcoholic fatty liver diseases (NAFLD), implying potential causality and underlying mechanism. Whether vitamin D supplement or treatment can improve these disorders is controversial, due in part to absence of large-scale trials. Experimental investigation on the other hand uncovered novel biological functions of vitamin D in development, tumor suppression, and immune regulation, far beyond its original role as a vitamin in maintaining calcium ho...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Conclusion The gene regulatory effect of PKM2 is involved in renal inflammation in type 2 diabetic nephropathy by promoting the phosphorylation of STAT3 and NF-kB and the expression of intercellular adhesion molecule 1. Thus, the down-regulation of phosphorylated PKM2 may have protective effects against diabetic nephropathy by inhibiting renal inflammation. [...] © Georg Thieme Verlag KG Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: Tags: Article Source Type: research
In conclusion, the present study suggested that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via Akt-HIF-α activation. PMID: 31905009 [PubMed - as supplied by publisher]
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Tags: Biochem Cell Biol Source Type: research
Publication date: Available online 22 November 2019Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Oktawia Nilsson, Rita Del Giudice, Mototsugu Nagao, Caitriona Grönberg, Lena Eliasson, Jens O. LagerstedtAbstractThe increase of plasma levels of high-density lipoproteins and Apolipoprotein A-I (ApoA-I), its main protein component, has been shown to have a positive action on glucose disposal in type 2 diabetic patients. The current study investigates the unexplored function of ApoA-I to prime beta cells for improved insulin secretion.INS-1E rat clonal beta cells as well as isolated mur...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
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