scholarly journals Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?

2020 ◽  
Vol 41 (3) ◽  
pp. 491-517 ◽  
Author(s):  
Alexis Diaz-Vegas ◽  
Pablo Sanchez-Aguilera ◽  
James R Krycer ◽  
Pablo E Morales ◽  
Matías Monsalves-Alvarez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Chronic Diseases ◽  
Metabolic Diseases ◽  
State Of The Art ◽  
Mitochondrial Damage ◽  
Targeted Therapeutics ◽  
Common Root

Abstract Mitochondrial damage is implicated as a major contributing factor for a number of noncommunicable chronic diseases such as cardiovascular diseases, cancer, obesity, and insulin resistance/type 2 diabetes. Here, we discuss the role of mitochondria in maintaining cellular and whole-organism homeostasis, the mechanisms that promote mitochondrial dysfunction, and the role of this phenomenon in noncommunicable chronic diseases. We also review the state of the art regarding the preclinical evidence associated with the regulation of mitochondrial function and the development of current mitochondria-targeted therapeutics to treat noncommunicable chronic diseases. Finally, we give an integrated vision of how mitochondrial damage is implicated in these metabolic diseases.

scholarly journals Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

2017 ◽  
Vol 233 (1) ◽  
pp. R15-R42 ◽  
Author(s):  
Sergio Di Meo ◽  
Susanna Iossa ◽  
Paola Venditti
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Early Event ◽  
Ros Production ◽  
Obese People ◽  
Skeletal Muscle Insulin Resistance ◽  
Mitochondrial Alterations

At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to ‘toxic’ lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.

scholarly journals Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7716
Author(s):  
Caterina Formichi ◽  
Laura Nigi ◽  
Giuseppina Emanuela Grieco ◽  
Carla Maccora ◽  
Daniela Fignani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases ◽  
Gene Expression Regulation ◽  
Biological Fluids ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

The rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application.

scholarly journals Macronutrient Determinants of Obesity, Insulin Resistance and Metabolic Health

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 336
Author(s):  
Jibran A. Wali ◽  
Samantha M. Solon-Biet ◽  
Therese Freire ◽  
Amanda E. Brandon
Keyword(s):  
Insulin Resistance ◽  
Dietary Intervention ◽  
Metabolic Diseases ◽  
Metabolic Health ◽  
Nutritional Science ◽  
Prevalence Of Obesity ◽  
Modifiable Factor

Obesity caused by the overconsumption of calories has increased to epidemic proportions. Insulin resistance is often associated with an increased adiposity and is a precipitating factor in the development of cardiovascular disease, type 2 diabetes, and altered metabolic health. Of the various factors contributing to metabolic impairments, nutrition is the major modifiable factor that can be targeted to counter the rising prevalence of obesity and metabolic diseases. However, the macronutrient composition of a nutritionally balanced “healthy diet” are unclear, and so far, no tested dietary intervention has been successful in achieving long-term compliance and reductions in body weight and associated beneficial health outcomes. In the current review, we briefly describe the role of the three major macronutrients, carbohydrates, fats, and proteins, and their role in metabolic health, and provide mechanistic insights. We also discuss how an integrated multi-dimensional approach to nutritional science could help in reconciling apparently conflicting findings.

scholarly journals Mechanism of insulin resistance in obesity: a role of ATP

2021 ◽  
Author(s):  
Jianping Ye
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Energy Demand ◽  
Feedback Regulation ◽  
Substrate Uptake ◽  
Atp Production ◽  
Systemic Insulin Resistance ◽  
Primary Signal

AbstractObesity increases the risk of type 2 diabetes through the induction of insulin resistance. The mechanism of insulin resistance has been extensively investigated for more than 60 years, but the essential pathogenic signal remains missing. Existing hypotheses include inflammation, mitochondrial dysfunction, hyperinsulinemia, hyperglucagonemia, glucotoxicity, and lipotoxicity. Drug discoveries based on these hypotheses are unsuccessful in the development of new medicines. In this review, multidisciplinary literature is integrated to evaluate ATP as a primary signal for insulin resistance. The ATP production is elevated in insulin-sensitive cells under obese conditions independent of energy demand, which we have named “mitochondrial overheating.” Overheating occurs because of substrate oversupply to mitochondria, leading to extra ATP production. The ATP overproduction contributes to the systemic insulin resistance through several mechanisms, such as inhibition of AMPK, induction of mTOR, hyperinsulinemia, hyperglucagonemia, and mitochondrial dysfunction. Insulin resistance represents a feedback regulation of energy oversupply in cells to control mitochondrial overloading by substrates. Insulin resistance cuts down the substrate uptake to attenuate mitochondrial overloading. The downregulation of the mitochondrial overloading by medicines, bypass surgeries, calorie restriction, and physical exercise leads to insulin sensitization in patients. Therefore, ATP may represent the primary signal of insulin resistance in the cellular protective response to the substrate oversupply. The prevention of ATP overproduction represents a key strategy for insulin sensitization.

scholarly journals Circulating Cell-Free mtDNA Contributes to AIM2 Inflammasome-Mediated Chronic Inflammation in Patients with Type 2 Diabetes

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 328 ◽  
Author(s):  
Jung Hwan Bae ◽  
Seung II Jo ◽  
Seong Jin Kim ◽  
Jong Min Lee ◽  
Ji Hun Jeong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mitochondrial Dysfunction ◽  
Chronic Inflammation ◽  
Healthy Subjects ◽  
Interleukin 1 ◽  
Prognosis Factors ◽  
Mitochondria Dna

Mitochondrial dysfunction has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. Damaged mitochondria DNA (mtDNA) may have a role in regulating hyperglycemia during type 2 diabetes. Circulating cell-free mitochondria DNA (ccf-mtDNA) was found in serum and plasma from patients and has been linked to the prognosis factors in various human diseases. However, the role of ccf-mtDNA in chronic inflammation in type 2 diabetes is unclear. In this study, we hypothesized that the ccf-mtDNA levels are associated with chronic inflammation in patients with type 2 diabetes. The mtDNA levels were elevated in the plasma from patients with type 2 diabetes compared to healthy subjects. The elevated mtDNA levels were associated with interleukin-1 (IL-1)β levels in patients with type 2 diabetes. The mtDNA, from patients with type 2 diabetes, induced absent in melanoma 2 (AIM2) inflammasome-dependent caspase-1 activation and IL-1β and IL-18 secretion in macrophages. Our results suggest that the ccf-mtDNA might contribute to AIM2 inflammasome-mediated chronic inflammation in type 2 diabetes.

scholarly journals THE ROLE OF AMPK AND MTOR IN THE DEVELOPMENT OF INSULIN RESISTANCE AND TYPE 2 DIABETES. THE MECHANISM OF METFORMIN ACTION (literature review)

2016 ◽  
Vol 57 (3) ◽  
pp. 77-90
Author(s):  
V. M. Pushkarev ◽  
L. K. Sokolova ◽  
V. V. Pushkarev ◽  
M. D. Tronko
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Literature Review ◽  
Metabolic Diseases ◽  
Mechanisms Of Action ◽  
Low Grade ◽  
Biochemical Mechanisms ◽  
Low Grade Inflammation

It was analyzed the cellular and molecular links between chronic low-grade inflammation and caused by inflammation insulin resistance and type 2 diabetes. Particular emphasis is placed on the participation of AMPK and mTORC1 in the development of metabolic diseases caused by obesity. A detailed analysis of the biochemical mechanisms of action of the main drug used in the treatment of insulin resistance and type 2 diabetes — metformin.

scholarly journals Early or advanced stage type 2 diabetes is not accompanied by in vivo skeletal muscle mitochondrial dysfunction

2008 ◽  
Vol 158 (5) ◽  
pp. 643-653 ◽  
Author(s):  
H M De Feyter ◽  
N M A van den Broek ◽  
S F E Praet ◽  
K Nicolay ◽  
L J C van Loon ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Resonance Spectroscopy ◽  
Diabetes Patients

ObjectiveSeveral lines of evidence support a potential role of skeletal muscle mitochondrial dysfunction in the pathogenesis of insulin resistance and/or type 2 diabetes. However, it remains to be established whether mitochondrial dysfunction represents either cause or consequence of the disease. We examined in vivo skeletal muscle mitochondrial function in early and advanced stages of type 2 diabetes, with the aim to gain insight in the proposed role of mitochondrial dysfunction in the aetiology of insulin resistance and/or type 2 diabetes.MethodsTen long-standing, insulin-treated type 2 diabetes patients, 11 subjects with impaired fasting glucose, impaired glucose tolerance and/or recently diagnosed type 2 diabetes, and 12 healthy, normoglycaemic controls, matched for age and body composition and with low habitual physical activity levels were studied. In vivo mitochondrial function of the vastus lateralis muscle was evaluated from post-exercise phosphocreatine (PCr) recovery kinetics using 31P magnetic resonance spectroscopy (MRS). Intramyocellular lipid (IMCL) content was assessed in the same muscle using single-voxel 1H MRS.ResultsIMCL content tended to be higher in the type 2 diabetes patients when compared with normoglycaemic controls (P=0.06). The31P MRS parameters for mitochondrial function, i.e. PCr and ADP recovery time constants and maximum aerobic capacity, did not differ between groups.ConclusionsThe finding that in vivo skeletal muscle oxidative capacity does not differ between long-standing, insulin-treated type 2 diabetes patients, subjects with early stage type 2 diabetes and sedentary, normoglycaemic controls suggests that mitochondrial dysfunction does not necessarily represent either cause or consequence of insulin resistance and/or type 2 diabetes.

1758-P: Type 2 Diabetes–Associated Mood Disorders: Role of Insulin Resistance in Serotonergic Neurons

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1758-P
Author(s):  
HUGO MARTIN ◽  
SÉBASTIEN BULLICH ◽  
FABIEN DUCROCQ ◽  
MARION GRALAND ◽  
CLARA OLIVRY ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Mood Disorders ◽  
Serotonergic Neurons ◽  
P Type

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients

2016 ◽  
Vol 22 (18) ◽  
pp. 2650-2656 ◽  
Author(s):  
Noelia Diaz-Morales ◽  
Susana Rovira-Llopis ◽  
Irene Escribano-Lopez ◽  
Celia Bañuls ◽  
Sandra Lopez-Domenech ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Type 2 Diabetic
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