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 The influence of sleep and sleep loss upon food intake and metabolism

2007 ◽  
Vol 20 (2) ◽  
pp. 195-212 ◽  
Author(s):  
Cibele Aparecida Crispim ◽  
Ioná Zalcman ◽  
Murilo Dáttilo ◽  
Heloisa Guarita Padilha ◽  
Ben Edwards ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Feedback Regulation ◽  
Modern Society ◽  
Blood Lipid ◽  
Sleep Time ◽  
Sleep Loss ◽  
The Body ◽  
Negative Feedback Regulation

The present review investigates the role of sleep and its alteration in triggering metabolic disorders. The reduction of the amount of time sleeping has become an endemic condition in modern society and the current literature has found important associations between sleep loss and alterations in nutritional and metabolic aspects. Studies suggest that individuals who sleep less have a higher probability of becoming obese. It can be related to the increase of ghrelin and decrease of leptin levels, generating an increase of appetite and hunger. Sleep loss has been closely associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and diabetes, and this disturbance may reflect decreased efficacy of the negative-feedback regulation of the hypothalamic–pituitary–adrenal axis. The period of sleep is also associated with an increase of blood lipid concentrations, which can be intensified under conditions of reduced sleep time, leading to disorders in fat metabolism. Based on a review of the literature, we conclude that sleep loss represents an important risk factor for weight gain, insulin resistance, type 2 diabetes and dyslipidaemia. Therefore, an adequate sleep pattern is fundamental for the nutritional balance of the body and should be encouraged by professionals in the area.

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 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 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 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

scholarly journals Magnesium, Little Known But Possibly Relevant: A Link between NASH and Related Comorbidities

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 125
Author(s):  
Jorge Simón ◽  
Teresa Cardoso Delgado ◽  
Luis Alfonso Martinez-Cruz ◽  
Maria Luz Martínez-Chantar
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Inflammatory Process ◽  
Fibrotic Response ◽  
Hepatic Lipid Accumulation ◽  
Root Cause ◽  
Worldwide Population ◽  
Global Health Problem

Non-alcoholic steatohepatitis (NASH) is characterized by an abnormal hepatic lipid accumulation accompanied by a necro-inflammatory process and a fibrotic response. It comprises from 10% to 30% of cases of patients with non-alcoholic liver disease, which is a global health problem affecting around a quarter of the worldwide population. Nevertheless, the development of NASH is often surrounded by a pathological context with other comorbidities, such as cardiovascular diseases, obesity, insulin resistance or type 2 diabetes mellitus. Dietary imbalances are increasingly recognized as the root cause of these NASH-related comorbidities. In this context, a growing concern exists about whether magnesium consumption in the general population is sufficient. Hypomagnesemia is a hallmark of the aforementioned NASH comorbidities, and deficiencies in magnesium are also widely related to the triggering of complications that aggravate NASH or derived pathologies. Moreover, the supplementation of this cation has proved to reduce mortality from hepatic complications. In the present review, the role of magnesium in NASH and related comorbidities has been characterized, unraveling the relevance of maintaining the homeostasis of this cation for the correct functioning of the organism.

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