Low cytochrome oxidase 4I1 links mitochondrial dysfunction to obesity and type 2 diabetes in humans and mice

2015 ◽  
Vol 39 (8) ◽  
pp. 1254-1263 ◽  
Author(s):  
B Van der Schueren ◽  
R Vangoitsenhoven ◽  
B Geeraert ◽  
D De Keyzer ◽  
M Hulsmans ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Cytochrome Oxidase

scholarly journals Transcriptional Profiling and Biological Pathway(s) Analysis of Type 2 Diabetes Mellitus in a Pakistani Population

2020 ◽  
Vol 17 (16) ◽  
pp. 5866
Author(s):  
Zarish Noreen ◽  
Christopher A. Loffredo ◽  
Attya Bhatti ◽  
Jyothirmai J. Simhadri ◽  
Gail Nunlee-Bland ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Health Concern ◽  
Receptor Signaling ◽  
Small Pilot Study

The epidemic of type 2 diabetes mellitus (T2DM) is an important global health concern. Our earlier epidemiological investigation in Pakistan prompted us to conduct a molecular investigation to decipher the differential genetic pathways of this health condition in relation to non-diabetic controls. Our microarray studies of global gene expression were conducted on the Affymetrix platform using Human Genome U133 Plus 2.0 Array along with Ingenuity Pathway Analysis (IPA) to associate the affected genes with their canonical pathways. High-throughput qRT-PCR TaqMan Low Density Array (TLDA) was performed to validate the selected differentially expressed genes of our interest, viz., ARNT, LEPR, MYC, RRAD, CYP2D6, TP53, APOC1, APOC2, CYP1B1, SLC2A13, and SLC33A1 using a small population validation sample (n = 15 cases and their corresponding matched controls). Overall, our small pilot study revealed a discrete gene expression profile in cases compared to controls. The disease pathways included: Insulin Receptor Signaling, Type II Diabetes Mellitus Signaling, Apoptosis Signaling, Aryl Hydrocarbon Receptor Signaling, p53 Signaling, Mitochondrial Dysfunction, Chronic Myeloid Leukemia Signaling, Parkinson’s Signaling, Molecular Mechanism of Cancer, and Cell Cycle G1/S Checkpoint Regulation, GABA Receptor Signaling, Neuroinflammation Signaling Pathway, Dopamine Receptor Signaling, Sirtuin Signaling Pathway, Oxidative Phosphorylation, LXR/RXR Activation, and Mitochondrial Dysfunction, strongly consistent with the evidence from epidemiological studies. These gene fingerprints could lead to the development of biomarkers for the identification of subgroups at high risk for future disease well ahead of time, before the actual disease becomes visible.

scholarly journals Muscular mitochondrial dysfunction and type 2 diabetes mellitus

2007 ◽  
Vol 10 (6) ◽  
pp. 698-703 ◽  
Author(s):  
Vera B Schrauwen-Hinderling ◽  
Michael Roden ◽  
M Eline Kooi ◽  
Matthijs KC Hesselink ◽  
Patrick Schrauwen
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction

Ubiquinone (coenzyme Q10) prevents renal mitochondrial dysfunction in an experimental model of type 2 diabetes

2012 ◽  
Vol 52 (3) ◽  
pp. 716-723 ◽  
Author(s):  
Karly C. Sourris ◽  
Brooke E. Harcourt ◽  
Peter H. Tang ◽  
Amy L. Morley ◽  
Karina Huynh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Experimental Model ◽  
Coenzyme Q10

scholarly journals Relationship Between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

2019 ◽  
Vol 8 (9) ◽  
pp. 1385 ◽  
Author(s):  
Burgos-Morón ◽  
Abad-Jiménez ◽  
Marañón ◽  
Iannantuoni ◽  
Escribano-López ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Current Knowledge ◽  
Β Cells ◽  
The Relationship ◽  
And Oxidative Stress

Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

scholarly journals Mitochondrial Dysfunction andβ-Cell Failure in Type 2 Diabetes Mellitus

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Zhongmin Alex Ma ◽  
Zhengshan Zhao ◽  
John Turk
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Membrane Integrity ◽  
Metabolic Stress ◽  
Atp Synthesis ◽  
Peripheral Insulin Resistance ◽  
Glucose Stimulated Insulin Secretion

Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic isletβ-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor toβ-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS) produced byβ-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead toβ-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reducedβ-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochromecrelease into cytosol and apoptosis. Group VIA phospholipase A2(iPLA2β) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increasesβ-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects onβ-cell mitochondrial phospholipids might prevent or retard development of T2DM.

scholarly journals Platelet Mitochondrial Dysfunction is Evident in Type 2 Diabetes in Association with Modifications of Mitochondrial Anti-Oxidant Stress Proteins

2011 ◽  
Vol 120 (04) ◽  
pp. 248-251 ◽  
Author(s):  
C. Avila ◽  
R. Huang ◽  
M. Stevens ◽  
A. Aponte ◽  
D. Tripodi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Oxidant Stress ◽  
Mitochondrial Protein ◽  
Protein Carbonylation ◽  
Mitochondrial Enzymes ◽  
Anti Oxidant ◽  
Type 2 Diabetic

AbstractMitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells.A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls.As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This ‘stress-signature’ in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as “accessible human tissue”, may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.

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