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

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 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 Interaction between Mitochondria and the Endoplasmic Reticulum: Implications for the Pathogenesis of Type 2 Diabetes Mellitus

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jaechan Leem ◽  
Eun Hee Koh
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Endoplasmic Reticulum ◽  
Type 2 Diabetes Mellitus ◽  
Er Stress ◽  
Mitochondrial Dysfunction ◽  
Apoptotic Cell ◽  
Peripheral Insulin Resistance ◽  
Type 2 Dm

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are closely associated withβ-cell dysfunction and peripheral insulin resistance. Thus, each of these factors contributes to the development of type 2 diabetes mellitus (DM). The accumulated evidence reveals structural and functional communications between mitochondria and the ER. It is now well established that ER stress causes apoptotic cell death by disturbing mitochondrial Ca2+homeostasis. In addition, recent studies have shown that mitochondrial dysfunction causes ER stress. In this paper, we summarize the roles that mitochondrial dysfunction and ER stress play in the pathogenesis of type 2 DM. Structural and functional communications between mitochondria and the ER are also discussed. Finally, we focus on recent findings supporting the hypothesis that mitochondrial dysfunction and the subsequent induction of ER stress play important roles in the pathogenesis of type 2 DM.

Role and clinical significance of lymphocyte mitochondrial dysfunction in type 2 diabetes mellitus

2011 ◽  
Vol 158 (6) ◽  
pp. 344-359 ◽  
Author(s):  
Saba Khan ◽  
Gorantla V. Raghuram ◽  
Arpit Bhargava ◽  
Neelam Pathak ◽  
Dolly H. Chandra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Clinical Significance

Association of mitochondrial dysfunction and lipid metabolism with type 2 diabetes mellitus: A review of literature

2018 ◽  
Vol 13 (6) ◽  
pp. 406-417
Author(s):  
Karimeh Haghani ◽  
Pouyan Asadi ◽  
Gholamreza Taheripak ◽  
Ali Noori-Zadeh ◽  
Shahram Darabi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Lipid Metabolism ◽  
Mitochondrial Dysfunction ◽  
Review Of Literature

P1016EMPAGLIFLOZIN REDUCES URINARY MITOCHONDRIAL DNA IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Haekyung Lee ◽  
Wonmi Yang ◽  
Hyoungnae Kim ◽  
Jin Seok Jeon ◽  
Hyunjin Noh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Healthy Volunteers ◽  
Quantitative Polymerase Chain Reaction ◽  
Sglt2 Inhibitors ◽  
Copy Numbers

Abstract Background and Aims Recent evidences has shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes of type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve clinical outcomes are unclear. Mitochondrial dysfunction plays a principal role in the pathophysiology of T2DM and its complications. We hypothesized empagliflozin, an SGLT2 inhibitor improves mitochondrial dysfunction in T2DM patients. Method We prospectively recruited healthy volunteers (n = 22) and SGLT2 naïve T2DM patients (n = 21). Copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured using quantitative polymerase chain reaction in healthy volunteers and T2DM patients at baseline and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Results Patients with T2DM were older than healthy volunteers and had higher body mass index and systolic blood pressure, but lower estimated glomerular filtration rate. Urinary mtND-1 and mtCOX-3 copy numbers were significantly higher in the T2DM group than in healthy volunteers. Urinary mtDNA copy numbers were correlated with diabetes duration (8.74 ± 7.60 years, r = 0.54, P = 0.01 for mtND-1, r = 0.50, P = 0.02 for mtCOX-3). Urinary copy numbers of mtND-1 and mtCOX-3 decreased after empagliflozin treatment. The amount of reduction of urinary mtDNA copy number did not differ according to empagliflozin dose (P = 0.897 for mtND-1, P = 0.462 for mtCOX-3). Conclusion In this study, we found that T2DM is associated with elevated urinary mtND-1 and mtCOX-3 copy numbers. Empagliflozin reduces the elevated urinary mtND-1 and mtCOX-3 copy numbers in patients with T2DM. Our results suggest that empagliflozin could attenuate mitochondrial damage in the kidney cells of T2DM patients.

scholarly journals Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis

2019 ◽  
Vol 316 (2) ◽  
pp. E268-E285 ◽  
Author(s):  
Mark V. Pinti ◽  
Garrett K. Fink ◽  
Quincy A. Hathaway ◽  
Andrya J. Durr ◽  
Amina Kunovac ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Epigenetic Modification ◽  
Peripheral Tissues ◽  
Energy Substrate ◽  
Mtdna Mutations ◽  
Organ Systems

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.

scholarly journals Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus

Life ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 348
Author(s):  
Vladimir Grubelnik ◽  
Jan Zmazek ◽  
Rene Markovič ◽  
Marko Gosak ◽  
Marko Marhl
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Mitochondrial Dysfunction ◽  
Beta Cells ◽  
Metabolic Diseases ◽  
Hormone Secretion ◽  
Glucagon Secretion ◽  
Mitochondrial Energy Metabolism

Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus. In the present study, we explore how mitochondrial dysfunction impairs the coupling between metabolism and exocytosis in the pancreatic alpha and beta cells. We demonstrate that reduced mitochondrial ATP production is linked with the observed defects in insulin and glucagon secretion by utilizing computational modeling approach. Specifically, a 30–40% reduction in alpha cells’ mitochondrial function leads to a pathological shift of glucagon secretion, characterized by oversecretion at high glucose concentrations and insufficient secretion in hypoglycemia. In beta cells, the impaired mitochondrial energy metabolism is accompanied by reduced insulin secretion at all glucose levels, but the differences, compared to a normal beta cell, are the most pronounced in hyperglycemia. These findings improve our understanding of metabolic pathways and mitochondrial bioenergetics in the pathology of type 2 diabetes mellitus and might help drive the development of innovative therapies to treat various metabolic diseases.

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