Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Mitochondrial Dysfunction In Type 2 Diabetes Mellitus: An Organ-based Analysis.

M. Pinti, Garrett K. Fink, Q. A. Hathaway, Andrya J. Durr, Amina Kunovac, J. Hollander
Published 2019 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Type 2 diabetes mellitus (T2DM) is a systemic disease characterized by hyperglycemia, hyperlipidemia, and organismic insulin resistance. This pathological shift in both circulating fuel levels and energy substrate utilization by central and peripheral tissues contributes to mitochondrial dysfunction across organ systems. The mitochondrion lies at the intersection of critical cellular pathways such as energy substrate metabolism, reactive oxygen species (ROS) generation, and apoptosis. It is the disequilibrium of these processes in T2DM that results in downstream deficits in vital functions, including hepatocyte metabolism, cardiac output, skeletal muscle contraction, β-cell insulin production, and neuronal health. Although mitochondria are known to be susceptible to a variety of genetic and environmental insults, the accumulation of mitochondrial DNA (mtDNA) mutations and mtDNA copy number depletion is helping to explain the prevalence of mitochondrial-related diseases such as T2DM. Recent work has uncovered novel mitochondrial biology implicated in disease progressions such as mtDNA heteroplasmy, noncoding RNA (ncRNA), epigenetic modification of the mitochondrial genome, and epitranscriptomic regulation of the mtDNA-encoded mitochondrial transcriptome. The goal of this review is to highlight mitochondrial dysfunction observed throughout major organ systems in the context of T2DM and to present new ideas for future research directions based on novel experimental and technological innovations in mitochondrial biology. Finally, the field of mitochondria-targeted therapeutics is discussed, with an emphasis on novel therapeutic strategies to restore mitochondrial homeostasis in the setting of T2DM.
This paper references
10.1016/j.jhep.2009.11.030
Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model.
R. Rector (2010)
10.1007/s00401-010-0697-7
Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy
A. M. Vincent (2010)
10.1152/japplphysiol.00921.2011
Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes.
J. Little (2011)
10.1016/j.expneurol.2005.07.012
CoQ10 therapy attenuates amyloid β-peptide toxicity in brain mitochondria isolated from aged diabetic rats
P. Moreira (2005)
10.2337/db13-1459
Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes
E. Nilsson (2014)
10.1038/nrg.2016.114
Detecting circular RNAs: bioinformatic and experimental challenges
Linda Szabo (2016)
10.2337/db13-1751
Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Is Required for Insulin Signaling and Is Implicated in Hepatic Insulin Resistance
E. Tubbs (2014)
10.1530/EJE-07-0756
Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction.
H. M. De Feyter (2008)
10.1073/pnas.1012311108
DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria
Lisa S. Shock (2011)
10.1007/s00125-007-0594-3
Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle
R. Boushel (2007)
10.1172/JCI37048
Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans.
E. Anderson (2009)
10.1007/s00125-006-0170-2
Mitochondria are impaired in the adipocytes of type 2 diabetic mice
HJ Choo (2006)
10.1016/J.MITO.2004.09.001
Mitochondrial genome polymorphisms associated with type-2 diabetes or obesity.
L. Guo (2005)
10.2337/DIABETES.53.9.2366
Impaired cardiac efficiency and increased fatty acid oxidation in insulin-resistant ob/ob mouse hearts.
P. K. Mazumder (2004)
10.1152/ajpheart.00932.2010
Increased propensity for cell death in diabetic human heart is mediated by mitochondrial-dependent pathways.
E. Anderson (2011)
10.1186/2049-3002-2-12
Metformin directly acts on mitochondria to alter cellular bioenergetics
S. Andrzejewski (2014)
10.1073/PNAS.0511154103
Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology.
Tianzheng Yu (2006)
10.2337/diab.47.2.276
New Mitochondrial DNA Homoplasmic Mutations Associated With Japanese Patients With Type 2 Diabetes
M. Tawata (1998)
10.2337/db16-0915
Metformin Suppresses Diabetes-Accelerated Atherosclerosis via the Inhibition of Drp1-Mediated Mitochondrial Fission
Qi-Long Wang (2016)
10.1038/35049533
DNA methylation in health and disease
K. Robertson (2000)
10.1038/NG0892-368
Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness
Jmw van den Ouweland (1992)
10.2337/db10-0818
Diminished Superoxide Generation Is Associated With Respiratory Chain Dysfunction and Changes in the Mitochondrial Proteome of Sensory Neurons From Diabetic Rats
Eli Akude (2010)
10.1152/ajpheart.00267.2010
Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes.
Erinne R. Dabkowski (2010)
10.1016/j.cellsig.2008.10.004
Coupling mitochondrial dysfunction to endoplasmic reticulum stress response: a molecular mechanism leading to hepatic insulin resistance.
J. Lim (2009)
10.1006/ABBI.2000.1829
Mitochondrial adaptations to obesity-related oxidant stress.
S. Yang (2000)
10.1002/dmrr.200
Brain and liver mitochondria isolated from diabeticGoto‐Kakizaki rats show different susceptibility to induced oxidative stress
M. S. Santos (2001)
10.1007/s004010050764
Reactive, degenerative, and proliferative Schwann cell responses in experimental galactose and human diabetic neuropathy
M. Kalichman (1997)
10.1007/s00125-008-0933-z
A mitochondrial DNA variant at position 16189 is associated with type 2 diabetes mellitus in Asians
K. Park (2008)
10.1016/J.CMET.2005.06.006
Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice.
S. Neschen (2005)
10.1620/TJEM.215.377
Novel mutations of mitochondrial DNA associated with type 2 diabetes in Chinese Han population.
W. Liao (2008)
10.2337/db08-0391
Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients
E. Phielix (2008)
10.1007/s00125-015-3829-8
Disruption of calcium transfer from ER to mitochondria links alterations of mitochondria-associated ER membrane integrity to hepatic insulin resistance
J. Rieusset (2015)
10.2337/db09-0259
Tissue-Specific Remodeling of the Mitochondrial Proteome in Type 1 Diabetic Akita Mice
H. Bugger (2009)
10.2337/db05-1421
Downregulation of Electron Transport Chain Genes in Visceral Adipose Tissue in Type 2 Diabetes Independent of Obesity and Possibly Involving Tumor Necrosis Factor-α
I. Dahlman (2006)
10.1038/s41467-018-03149-4
scNMT-seq enables joint profiling of chromatin accessibility DNA methylation and transcription in single cells
Stephen J Clark (2018)
10.1038/s41598-017-15589-x
Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes
M. Ward (2017)
10.1038/nm.3735
Chronic enrichment of hepatic endoplasmic reticulum–mitochondria contact leads to mitochondrial dysfunction in obesity
Ana Paula Arruda (2014)
10.1002/hep.23927
Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator–activated receptor γ coactivator 1α promoter
S. Sookoian (2010)
10.1016/j.redox.2017.01.013
Mitochondrial dynamics in type 2 diabetes: Pathophysiological implications
S. Rovira-Llopis (2017)
10.1038/nrg3642
Sequencing depth and coverage: key considerations in genomic analyses
D. Sims (2014)
10.1074/jbc.274.9.5692
Obesity Induces Expression of Uncoupling Protein-2 in Hepatocytes and Promotes Liver ATP Depletion*
K. Chavin (1999)
10.1210/jc.2010-1621
Skeletal muscle mitochondrial capacity and insulin resistance in type 2 diabetes.
S. Bajpeyi (2011)
10.1073/PNAS.95.5.2498
Fatty acid-induced β cell apoptosis: A link between obesity and diabetes
M. Shimabukuro (1998)
10.2337/db06-1135
Adipose Mitochondrial Biogenesis Is Suppressed in db/db and High-Fat Diet–Fed Mice and Improved by Rosiglitazone
J. X. Rong (2007)
10.1152/ajpendo.00703.2009
Changes in skeletal muscle mitochondria in response to the development of type 2 diabetes or prevention by daily wheel running in hyperphagic OLETF rats.
R. Rector (2010)
10.1007/s11010-014-2076-5
Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes
R. X. Santos (2014)
10.1038/nature12433
Charting a dynamic DNA methylation landscape of the human genome
Michael J. Ziller (2013)
10.1186/s12929-017-0375-3
Role of mitochondrial dysfunction and dysregulation of Ca2+ homeostasis in the pathophysiology of insulin resistance and type 2 diabetes
Chih-Hao Wang (2017)
10.2337/db11-1369
Mitochondrial DNA Coding and Control Region Variants as Genetic Risk Factors for Type 2 Diabetes
C. Liou (2012)
10.1038/nrg.2016.20
Endogenous microRNA sponges: evidence and controversy
Daniel W. Thomson (2016)
10.2337/DIABETES.51.6.1913
Gene expression profile in skeletal muscle of type 2 diabetes and the effect of insulin treatment.
R. Sreekumar (2002)
10.1007/s00439-005-0046-4
Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns
K. Mohlke (2005)
10.2337/DIABETES.54.1.8
Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes.
V. Ritov (2005)
10.1016/j.bbabio.2010.02.003
4Pi microscopy reveals an impaired three-dimensional mitochondrial network of pancreatic islet beta-cells, an experimental model of type-2 diabetes.
A. Dlasková (2010)
10.1016/j.neurobiolaging.2012.02.006
Effect of aging on 5-hydroxymethylcytosine in brain mitochondria
S. Dzitoyeva (2012)
10.1113/jphysiol.2013.270538
Impairments in mitochondrial palmitoyl‐CoA respiratory kinetics that precede development of diabetic cardiomyopathy are prevented by resveratrol in ZDF rats
Marie-Soleil Beaudoin (2014)
10.2337/DIABETES.49.7.1269
A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic mutation for maternally inherited type 2 diabetes.
M. Tawata (2000)
10.1126/SCIENCE.1104343
Mitochondrial Dysfunction and Type 2 Diabetes
B. Lowell (2005)
10.1038/emboj.2011.503
DNA methylation profiling identifies epigenetic dysregulation in pancreatic islets from type 2 diabetic patients
Michael Volkmar (2012)
10.1186/gb-2014-15-4-r54
DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns
Kaie Lokk (2013)
10.1186/1471-2350-10-60
Parental diabetes status reveals association of mitochondrial DNA haplogroup J1 with type 2 diabetes
J. Feder (2009)
10.1016/j.bbadis.2015.05.001
Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers.
C. Carvalho (2015)
10.1093/AJCN/8.5.740
Non-Esterified Fatty Acids in the Blood of Obese and Lean Subjects
E. Gordon (1960)
10.1172/JCI32601
Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice.
C. Bonnard (2008)
10.1016/S0006-291X(02)02832-2
Mitochondrial reactive oxygen species reduce insulin secretion by pancreatic β-cells
K. Sakai (2003)
10.1161/CIRCULATIONAHA.113.008476
Myocardial Contractile Dysfunction Is Associated With Impaired Mitochondrial Function and Dynamics in Type 2 Diabetic but Not in Obese Patients
D. Montaigne (2014)
10.1038/nm1044
PGC-1 promotes insulin resistance in liver through PPAR-α-dependent induction of TRB-3
Seung-Hoi Koo (2004)
10.1136/jcp.53.6.466
Presence of mitochondrial tRNA Leu(UUR) A to G 3243 mutation in DNA extracted from serum and plasma of patients with type 2 diabetes mellitus
S. Zhong (2000)
10.1038/nrg3198
MicroRNA profiling: approaches and considerations
C. Pritchard (2012)
10.1161/CIRCRESAHA.112.267732
Nuclear miRNA Regulates the Mitochondrial Genome in the Heart
Samarjit Das (2012)
10.1152/ajpheart.00267.2009
Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice.
T. Yokota (2009)
10.1016/j.molcel.2017.10.019
Base-Resolution Mapping Reveals Distinct m1A Methylome in Nuclear- and Mitochondrial-Encoded Transcripts.
X. Li (2017)
10.1038/ncb1596
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
H. Valadi (2007)
10.1016/j.redox.2016.12.022
The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1
L. Xiao (2017)
10.1016/j.tcb.2017.02.004
Mitochondria and Epigenetics - Crosstalk in Homeostasis and Stress.
O. Matilainen (2017)
10.1016/j.yjmcc.2018.04.016
Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus.
D. Shepherd (2018)
10.1073/pnas.0707060104
Mitochondrial dysfunction due to long-chain Acyl-CoA dehydrogenase deficiency causes hepatic steatosis and hepatic insulin resistance
Dongyan Zhang (2007)
10.1530/JOE-12-0356
Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes.
L. M. Hinder (2013)
10.2337/db07-0481
Mitochondrial Energetics in the Heart in Obesity-Related Diabetes
S. Boudina (2007)
10.1002/hep.23093
Abnormal hepatic energy homeostasis in type 2 diabetes
J. Szendroedi (2009)
10.1073/pnas.0914843107
Functional delivery of viral miRNAs via exosomes
D. M. Pegtel (2010)
10.1016/j.yjmcc.2017.06.012
Exploring the mitochondrial microRNA import pathway through Polynucleotide Phosphorylase (PNPase).
D. Shepherd (2017)
10.1172/JCI13505
Role of AMP-activated protein kinase in mechanism of metformin action.
G. Zhou (2001)
10.2337/DIABETES.54.SUPPL_2.S108
Mechanisms of β-Cell Death in Type 2 Diabetes
M. Donath (2005)
10.1093/brain/aws097
Impaired adenosine monophosphate-activated protein kinase signalling in dorsal root ganglia neurons is linked to mitochondrial dysfunction and peripheral neuropathy in diabetes.
Subir K. Roy Chowdhury (2012)
10.1074/JBC.275.5.3343
Effects of Aging on Mitochondrial DNA Copy Number and Cytochromec Oxidase Gene Expression in Rat Skeletal Muscle, Liver, and Heart*
R. Barazzoni (2000)
10.1002/dmrr.656
Low‐intensity exercise increases skeletal muscle protein expression of PPARδ and UCP3 in type 2 diabetic patients
T. Fritz (2006)
10.1016/j.mito.2014.07.007
Comparative analysis of human mitochondrial methylomes shows distinct patterns of epigenetic regulation in mitochondria.
S. Ghosh (2014)
10.1096/fj.03-1065fje
Triacylglycerol accumulation in human obesity and type 2 diabetes is associated with increased rates of skeletal muscle fatty acid transport and increased sarcolemmal FAT/CD36
A. Bonen (2004)
10.1073/PNAS.97.21.11371
The expression of adipogenic genes is decreased in obesity and diabetes mellitus.
S. Nadler (2000)
10.1101/gad.276022.115
HuR and GRSF1 modulate the nuclear export and mitochondrial localization of the lncRNA RMRP.
Ji Heon Noh (2016)
10.1210/jc.2011-3454
Physical activity is the key determinant of skeletal muscle mitochondrial function in type 2 diabetes.
F. V. van Tienen (2012)
10.1210/jc.2012-3093
Clinical Review: Nonalcoholic fatty liver disease: a novel cardiometabolic risk factor for type 2 diabetes and its complications.
G. Targher (2013)
10.1002/1873-3468.12440
Integrative analysis of Arabidopsis thaliana transcriptomics reveals intuitive splicing mechanism for circular RNA
Xiaoyong Sun (2016)
10.2337/DC06-1539
Spectrum of Liver Disease in Type 2 Diabetes and Management of Patients With Diabetes and Liver Disease
K. G. Tolman (2007)
10.1007/s00125-013-2945-6
The association of the mitochondrial DNA OriB variant (16184–16193 polycytosine tract) with type 2 diabetes in Europid populations
Z. Ye (2013)
10.1016/j.cmet.2015.04.004
Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis.
C. Koliaki (2015)
10.1038/NG0492-11
Maternally transmitted diabetes and deafness associated with a 10.4 kb mitochondrial DNA deletion
S. Ballinger (1992)
10.1152/AJPENDO.00590.2006
Increased intrahepatic triglyceride is associated with peripheral insulin resistance: in vivo MR imaging and spectroscopy studies.
J. Hwang (2007)
10.1007/s00125-009-1553-y
Diabetes regulates mitochondrial biogenesis and fission in mouse neurons
J. L. Edwards (2009)
10.1038/nm.2049
Foxo1 integrates insulin signaling with mitochondrial function in the liver
Z. Cheng (2009)
10.1038/nature14614
Mitochondrial reticulum for cellular energy distribution in muscle
B. Glancy (2015)
10.1002/(SICI)1096-9136(199701)14:1<42::AID-DIA295>3.0.CO;2-T
UKPDS 21: Low Prevalence of the Mitochondrial Transfer RNA gene (tRNA Leu(UUR)) Mutation at Position 3243bp in UK Caucasian Type 2 Diabetic Patients
P. J. Saker (1997)
10.1152/ajpheart.00845.2013
Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart.
T. L. Croston (2014)
10.1007/s00125-004-1627-9
Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients
M. Anello (2004)
10.2337/db09-1322
Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity
R. Meex (2009)
10.1073/pnas.061013598
Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication
Y. Wang (2001)
10.1038/ncb2441
Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs
Eduard Hergenreider (2012)
10.1016/j.metabol.2011.04.015
Mitochondrial bioenergetics is not impaired in nonobese subjects with type 2 diabetes mellitus.
Mrittika Chattopadhyay (2011)
10.2337/db10-0281
FTO Is Increased in Muscle During Type 2 Diabetes, and Its Overexpression in Myotubes Alters Insulin Signaling, Enhances Lipogenesis and ROS Production, and Induces Mitochondrial Dysfunction
Amélie Bravard (2010)
10.1086/512202
Mitochondrial haplogroup N9a confers resistance against type 2 diabetes in Asians.
N. Fuku (2007)
10.1016/j.celrep.2017.03.063
Power Grid Protection of the Muscle Mitochondrial Reticulum.
B. Glancy (2017)
10.1002/prp2.393
Effect of a mitochondrial‐targeted coenzyme Q analog on pancreatic β‐cell function and energetics in high fat fed obese mice
Y. Imai (2018)
10.1038/srep23421
CpG methylation patterns of human mitochondrial DNA
B. Liu (2016)
10.1016/J.CMET.2005.05.004
Metabolic control through the PGC-1 family of transcription coactivators.
J. Lin (2005)
10.1038/nature07534
Mitofusin 2 tethers endoplasmic reticulum to mitochondria
O. Brito (2008)
10.1172/JCI117790
Increased expression of mitochondrial-encoded genes in skeletal muscle of humans with diabetes mellitus.
D. Antonetti (1995)
10.1007/s00125-006-0475-1
Impaired in vivo mitochondrial function but similar intramyocellular lipid content in patients with type 2 diabetes mellitus and BMI-matched control subjects
V. Schrauwen-Hinderling (2006)
10.1016/S1097-2765(05)00015-8
Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction.
M. Michael (2000)
10.1152/ajpheart.00865.2013
Chronic inhibition of phosphodiesterase 5 with tadalafil attenuates mitochondrial dysfunction in type 2 diabetic hearts: potential role of NO/SIRT1/PGC-1α signaling.
S. Koka (2014)
10.1007/s00125-007-0867-x
Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome
A. Kotronen (2007)
10.1530/EC-14-0092
Mitochondrial dysfunction and insulin resistance: an update
M. Montgomery (2015)
10.1152/ajpregu.00423.2010
Proteomic alterations of distinct mitochondrial subpopulations in the type 1 diabetic heart: contribution of protein import dysfunction.
Walter A. Baseler (2011)
10.1016/j.jacc.2009.07.031
Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart.
E. Anderson (2009)
10.1056/NEJM199404073301403
A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA.
T. Kadowaki (1994)
10.1042/BJ3480607
Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain.
Marc R. Owen (2000)
10.1186/1755-8166-7-S1-P86
Comparative analysis of human mitochondrial methylome show distinct patterns of epigenetic regulation in mitochondria
S. Ghosh (2014)
10.1111/j.1469-1809.2005.00249.x
The European‐Specific Mitochondrial Cluster J/T Could Confer an Increased Risk of Insulin‐Resistance and Type 2 Diabetes: An Analysis of the m.4216T > C and m.4917A > G Variants
D. Crispim (2006)
10.1007/s00125-004-1605-2
Pancreatic beta cell senescence contributes to the pathogenesis of type 2 diabetes in high-fat diet-induced diabetic mice
H. Sone (2004)
10.1038/nmeth.3321
Quantitative gene profiling of long noncoding RNAs with targeted RNA sequencing
M. B. Clark (2015)
10.1007/s11010-014-2236-7
Enhanced ROS production and oxidative damage in subcutaneous white adipose tissue mitochondria in obese and type 2 diabetes subjects
Mrittika Chattopadhyay (2014)
10.1152/AJPENDO.00255.2001
Reduced activity of mtTFA decreases the transcription in mitochondria isolated from diabetic rat heart.
A. Kanazawa (2002)
10.1073/PNAS.91.23.10878
Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships.
Y. Lee (1994)
10.1016/j.tig.2015.03.009
Mitochondrial epigenetics: an overlooked layer of regulation?
Monique G P van der Wijst (2015)
10.1161/CIRCGENETICS.115.001067
Translational Regulation of the Mitochondrial Genome Following Redistribution of Mitochondrial MicroRNA in the Diabetic Heart
R. Jagannathan (2015)
10.1152/ajpendo.00407.2016
Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.
Stephan Nieuwoudt (2017)
10.1172/JCI117600
Impaired free fatty acid utilization by skeletal muscle in non-insulin-dependent diabetes mellitus.
D. Kelley (1994)
10.1042/BJ20140620
Effects of metformin and other biguanides on oxidative phosphorylation in mitochondria
H. R. Bridges (2014)
10.1146/annurev-pharmtox-010716-104908
Repairing Mitochondrial Dysfunction in Disease.
V. Sorrentino (2018)
Relationship between mutations of mitochondrial DNA ND1 gene and type 2 diabetes.
P. Yu (2004)
10.1016/j.bbabio.2016.02.014
The electrochemical transmission in I-Band segments of the mitochondrial reticulum.
K. Patel (2016)
10.1038/nmeth.3728
Parallel single-cell sequencing links transcriptional and epigenetic heterogeneity
Christof Angermueller (2016)
10.1016/S0092-8674(00)81656-6
DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development
M. Okano (1999)
10.2337/DIABETES.54.3.603
Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes.
K. Petersen (2005)
10.1016/j.cell.2015.01.012
Hepatic Acetyl CoA Links Adipose Tissue Inflammation to Hepatic Insulin Resistance and Type 2 Diabetes
Rachel J. Perry (2015)
10.1210/me.2012-1004
Increased DNA methylation and decreased expression of PDX-1 in pancreatic islets from patients with type 2 diabetes.
B. Yang (2012)
10.1152/ajpendo.00159.2011
Tissue-specific control of mitochondrial respiration in obesity-related insulin resistance and diabetes.
Maria H. Holmström (2012)
10.1038/ncomms1285
Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells
M. Mittelbrunn (2011)
10.1093/AJCN/87.2.295
Increased fat accumulation in liver may link insulin resistance with subcutaneous abdominal adipocyte enlargement, visceral adiposity, and hypoadiponectinemia in obese individuals.
J. Koška (2008)
10.1074/JBC.271.42.26194
Mitochondrial DNA Is Required for Regulation of Glucose-stimulated Insulin Secretion in a Mouse Pancreatic Beta Cell Line, MIN6*
A. Soejima (1996)
10.1152/ajpcell.00234.2013
Coronary endothelial dysfunction and mitochondrial reactive oxygen species in type 2 diabetic mice.
Y. Cho (2013)
10.2337/DIABETES.51.4.1256
Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study.
R. Peila (2002)
10.1007/s00125-008-1054-4
Age-related decline in mitochondrial DNA copy number in isolated human pancreatic islets
L. M. Cree (2008)
10.1038/ng1180
PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
V. Mootha (2003)
10.1093/cvr/cvp305
NF-kappaB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes.
N. Mariappan (2010)
10.1007/BF00703130
The effects of physical training on insulin secretion and effectiveness and on glucose metabolism in obesity and Type 2 (non-insulin-dependent) diabetes mellitus
M. Krotkiewski (2004)
10.1016/J.NUMECD.2005.09.004
Effects of moderate-intensity exercise training on plasma biomarkers of inflammation and endothelial dysfunction in older patients with type 2 diabetes.
G. Zoppini (2006)
10.1021/bi3015983
Effect of calcium on the oxidative phosphorylation cascade in skeletal muscle mitochondria.
B. Glancy (2013)
10.1053/j.gastro.2008.03.021
Increased liver fat, impaired insulin clearance, and hepatic and adipose tissue insulin resistance in type 2 diabetes.
A. Kotronen (2008)
10.1016/j.tem.2011.12.008
Linking mitochondrial bioenergetics to insulin resistance via redox biology
Kelsey H. Fisher-Wellman (2012)
10.1111/j.1463-1326.2004.00439.x
Molecular mechanisms of lipid‐induced insulin resistance in muscle, liver and vasculature
M. Krebs (2005)
10.1186/s13059-016-0950-z
Simultaneous profiling of transcriptome and DNA methylome from a single cell
Youjin Hu (2016)
10.3389/fendo.2018.00211
Mitochondrial Dynamics in Type 2 Diabetes and Cancer
M. Williams (2018)
10.1111/nyas.12016
Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals
Howard C. Masuoka (2013)
10.1161/ATVBAHA.112.256024
Adverse Alterations in Mitochondrial Function Contribute to Type 2 Diabetes Mellitus–Related Endothelial Dysfunction in Humans
T. Kizhakekuttu (2012)
10.1016/J.DIABRES.2005.12.001
Variation of mitochondrial gene and the association with type 2 diabetes mellitus in a Chinese population.
D. Tang (2006)
10.2337/DIACARE.26.3.725
The diabetes risk score: a practical tool to predict type 2 diabetes risk.
J. Lindström (2003)
10.1038/ncb2868
The physiological role of mitochondrial calcium revealed by mice lacking the mitochondrial calcium uniporter (MCU)
X. Pan (2013)
10.1038/nature03047
Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes
C. Wolfrum (2004)
10.2337/DIABETES.51.10.2944
Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes.
D. Kelley (2002)
10.1007/s00125-010-1813-x
Effect of physical training on mitochondrial respiration and reactive oxygen species release in skeletal muscle in patients with obesity and type 2 diabetes
M. Hey-Mogensen (2010)
10.1101/gr.077479.108
An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs).
V. Rakyan (2008)
10.2337/DIABETES.53.4.1052
Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions?
B. Brunmair (2004)
10.1161/CIRCHEARTFAILURE.111.961565
p53 Promotes Cardiac Dysfunction in Diabetic Mellitus Caused by Excessive Mitochondrial Respiration-Mediated Reactive Oxygen Species Generation and Lipid Accumulation
H. Nakamura (2012)
10.18388/ABP.2010_2422
Liver mitochondria and insulin resistance.
G. Vial (2010)
10.1016/J.CMET.2006.11.003
Hypomorphic mutation of PGC-1beta causes mitochondrial dysfunction and liver insulin resistance.
Claudia R. Vianna (2006)
10.1016/j.yjmcc.2015.01.012
The mitochondrial lncRNA ASncmtRNA-2 is induced in aging and replicative senescence in Endothelial Cells.
V. Bianchessi (2015)
10.1073/pnas.1032913100
Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1
M. Patti (2003)
10.1172/JCI70577
Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy.
C. Bang (2014)
10.1074/JBC.M212881200
Proteome Analysis Reveals Phosphorylation of ATP Synthase β-Subunit in Human Skeletal Muscle and Proteins with Potential Roles in Type 2 Diabetes*
K. Højlund (2003)
10.1089/ars.2016.6844
Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress.
T. Kamalden (2017)
10.1210/JC.2007-1734
Short-term exercise improves beta-cell function and insulin resistance in older people with impaired glucose tolerance.
C. Bloem (2008)
10.1007/s00125-015-3741-2
High intensity intermittent exercise improves cardiac structure and function and reduces liver fat in patients with type 2 diabetes: a randomised controlled trial
S. Cassidy (2015)
10.2337/db06-0981
Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes
M. Mogensen (2007)
10.2337/db12-0072
GSH or Palmitate Preserves Mitochondrial Energetic/Redox Balance, Preventing Mechanical Dysfunction in Metabolically Challenged Myocytes/Hearts From Type 2 Diabetic Mice
C. G. Tocchetti (2012)
10.1159/000373947
Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain
H. Raza (2015)
10.2337/db07-0141
Effects of Physical Activity and Weight Loss on Skeletal Muscle Mitochondria and Relationship With Glucose Control in Type 2 Diabetes
F. G. Toledo (2007)
10.1055/S-2001-17407
Association of the mitochondrial DNA 5178A/C polymorphism with maternal inheritance and onset of type 2 diabetes in Japanese patients.
D. Wang (2001)
10.1038/nature13478
The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Rachel J. Perry (2014)
10.1093/jb/mvn105
Saturated fatty acids inhibit hepatic insulin action by modulating insulin receptor expression and post-receptor signalling.
M. Ruddock (2008)
10.1161/CIRCULATIONAHA.110.014506
Altered Mitochondrial Dynamics Contributes to Endothelial Dysfunction in Diabetes Mellitus
S. Shenouda (2011)
10.1038/nature24456
The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution
Modi Safra (2017)
10.1001/archneurol.2010.225
Insulin resistance and Alzheimer-like reductions in regional cerebral glucose metabolism for cognitively normal adults with prediabetes or early type 2 diabetes.
L. Baker (2011)
10.1016/j.mce.2010.01.039
Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes
Chun-lin Gao (2010)
10.2337/DIABETES.52.6.1449
Increased vulnerability of brain mitochondria in diabetic (Goto-Kakizaki) rats with aging and amyloid-beta exposure.
P. Moreira (2003)
10.1113/jphysiol.2009.172601
Changes in visceral adipose tissue mitochondrial content with type 2 diabetes and daily voluntary wheel running in OLETF rats
M. Laye (2009)
10.1016/j.bbabio.2014.08.006
Stimulation of oxidative phosphorylation by calcium in cardiac mitochondria is not influenced by cAMP and PKA activity.
Raúl Covian (2014)
10.1016/j.redox.2016.10.017
The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients
I. Escribano-López (2016)
10.1016/J.DIABRES.2007.09.020
Improved endothelial function following a 14-month resistance exercise training program in adults with type 2 diabetes.
N. Cohen (2008)
10.2337/DIABETES.55.03.06.DB05-0934
Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats.
J. Cheng (2006)
10.1016/J.JDIACOMP.2005.07.005
Exercise training can modify the natural history of diabetic peripheral neuropathy.
S. Balducci (2006)
10.1261/rna.029405.111
Long noncoding RNAs are generated from the mitochondrial genome and regulated by nuclear-encoded proteins.
O. Rackham (2011)
10.1152/ajpendo.00317.2009
Deficiency of electron transport chain in human skeletal muscle mitochondria in type 2 diabetes mellitus and obesity.
V. Ritov (2010)
10.1371/journal.pone.0115433
Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function
Donna L. Nile (2014)
10.1126/SCIENCE.1112125
Mitochondrial DNA Mutations, Oxidative Stress, and Apoptosis in Mammalian Aging
G. Kujoth (2005)
10.1210/JC.2006-0653
A common mitochondrial DNA variant and increased body mass index as associated factors for development of type 2 diabetes: Additive effects of genetic and environmental factors.
C. Liou (2007)
10.1093/HMG/11.13.1581
Type 2 diabetes is associated with a common mitochondrial variant: evidence from a population-based case-control study.
J. Poulton (2002)
10.2337/db05-1230
Skeletal Muscle Mitochondrial Functions, Mitochondrial DNA Copy Numbers, and Gene Transcript Profiles in Type 2 Diabetic and Nondiabetic Subjects at Equal Levels of Low or High Insulin and Euglycemia
Y. Asmann (2006)
10.2337/dc10-1076
Liver ATP Synthesis Is Lower and Relates to Insulin Sensitivity in Patients With Type 2 Diabetes
A. I. Schmid (2011)
10.2337/db17-0316
Disruption of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Integrity Contributes to Muscle Insulin Resistance in Mice and Humans
E. Tubbs (2018)
10.1038/ncpendmet0190
Mechanisms of Disease: hepatic steatosis in type 2 diabetes—pathogenesis and clinical relevance
M. Roden (2006)
10.1038/NG1292-324
Mitochondrial DNA deletions in human brain: regional variability and increase with advanced age
M. Corral-Debrinski (1992)
10.2337/DIABETES.53.5.1336
Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes.
Gang Ye (2004)



This paper is referenced by
10.1096/fj.201902594RR
Mitochondrial adaptations to exercise do not require Bcl2‐mediated autophagy but occur with BNIP3/Parkin activation
Sarah E. Ehrlicher (2020)
10.1016/j.fct.2019.111082
T-2 toxin-induced DRP-1-dependent mitophagy leads to the apoptosis of mice Leydig cells (TM3).
J. Wu (2019)
10.3390/ijms20194748
Proposed Tandem Effect of Physical Activity and Sirtuin 1 and 3 Activation in Regulating Glucose Homeostasis
F. Pacifici (2019)
10.1016/j.freeradbiomed.2020.10.320
Hyperoside from Z. bungeanum leaves restores insulin secretion and mitochondrial function by regulating pancreatic cellular redox status in diabetic mice.
Yali Zhang (2020)
10.1016/j.redox.2020.101517
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions
N. Apostolova (2020)
10.1016/j.stemcr.2020.04.003
Modeling Hypoxia-Induced Neuropathies Using a Fast and Scalable Human Motor Neuron Differentiation System
Laura I. Hudish (2020)
10.1080/24701394.2020.1856101
Mitochondrial ND1 T4216C and ND2 C5178A mutations are associated with maternally transmitted diabetes mellitus.
Z. Jiang (2020)
10.1042/BST20190280
Impact of pharmacological agents on mitochondrial function: a growing opportunity?
M. Stoker (2019)
10.3389/fimmu.2020.01582
The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System
Gholamreza Daryabor (2020)
10.3389/fendo.2020.573032
Cellular Senescence as the Pathogenic Hub of Diabetes-Related Wound Chronicity
J. Berlanga-Acosta (2020)
10.1016/j.yjmcc.2020.03.016
Human induced pluripotent stem cell-derived cardiomyocytes reveal abnormal TGFβ signaling in type 2 diabetes mellitus.
L. Tang (2020)
10.1111/jcmm.15238
Enhanced liver but not muscle OXPHOS in diabetes and reduced glucose output by complex I inhibition
Miriayi Alimujiang (2020)
10.1016/j.mrrev.2020.108343
Chromosomal damage measured by the cytokinesis block micronucleus cytome assay in diabetes and obesity - A systematic review and meta-analysis.
Bernhard Franzke (2020)
10.1210/endrev/bnaa005
Is mitochondrial dysfunction a common root of noncommunicable chronic diseases?
A. Díaz-Vegas (2020)
10.3390/jcm9051446
Mitochondrial Dysfunction: A Common Hallmark Underlying Comorbidity between sIBM and Other Degenerative and Age-Related Diseases
M. Catalán‐García (2020)
10.1016/j.bbrc.2020.03.180
Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice.
Y. Arao (2020)
10.1186/s12933-019-0879-0
Machine-learning to stratify diabetic patients using novel cardiac biomarkers and integrative genomics
Q. A. Hathaway (2019)
10.1016/j.tem.2020.03.004
Mitochondria and T2D: Role of Autophagy, ER Stress, and Inflammasome
M. Rocha (2020)
10.1016/j.exer.2019.107789
pH balance and lactic acid increase in the vitreous body of diabetes mellitus patients.
Hiroki Mieno (2019)
10.3390/ijms21186559
Diabetes Mellitus, Mitochondrial Dysfunction and Ca2+-Dependent Permeability Transition Pore
K. Belosludtsev (2020)
10.3389/fcell.2020.571554
Mitochondria-Associated Endoplasmic Reticulum Membranes in the Pathogenesis of Type 2 Diabetes Mellitus
Shanshan Yang (2020)
10.1111/jfbc.13443
Proteomic analysis of liver mitochondria of db/db mice treated with grape seed procyanidin B2.
F. Yu (2020)
10.1152/ajprenal.00181.2019
Diabetes aggravates renal ischemia reperfusion injury by repressing mitochondrial function and PINK1/Parkin-mediated mitophagy.
Yuanyuan Yang (2019)
10.1111/cge.13749
Primrose syndrome: Characterization of the phenotype in 42 patients
D. Melis (2020)
10.1093/jn/nxaa146
Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults.
Keming Yang (2020)
10.1038/s41598-020-77621-x
Alpha lipoic acid attenuates ER stress and improves glucose uptake through DNAJB3 cochaperone
A. Diané (2020)
10.3390/antiox9090820
Methylglyoxal-Induced Dysfunction in Brain Endothelial Cells via the Suppression of Akt/HIF-1α Pathway and Activation of Mitophagy Associated with Increased Reactive Oxygen Species
D. Kim (2020)
10.1007/s11154-020-09549-6
Current perspectives of oleic acid: Regulation of molecular pathways in mitochondrial and endothelial functioning against insulin resistance and diabetes
Kanwal Rehman (2020)
10.1016/j.acvd.2020.06.006
Myocardial glucotoxicity: Mechanisms and potential therapeutic targets.
S. Battault (2020)
10.1016/j.bbamcr.2020.118805
The balancing act of NEET proteins: Iron, ROS, calcium and metabolism.
R. Nechushtai (2020)
10.1007/s11154-020-09545-w
Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm
Jacob Bar-Tana (2020)
10.3390/cells9061553
Amyloid Proteins and Peripheral Neuropathy
Mohammed M H Asiri (2020)
See more
Semantic Scholar Logo Some data provided by SemanticScholar