scholarly journals Mitochondrial destiny in type 2 diabetes: the effects of oxidative stress on the dynamics and biogenesis of mitochondria

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9741 ◽  
Author(s):  
Daria Skuratovskaia ◽  
Alexandra Komar ◽  
Maria Vulf ◽  
Larisa Litvinova
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Nuclease Activity ◽  
Main Role ◽  
Mtdna Copy Number ◽  
Mitochondrial Proteome ◽  
Insulin Dependent ◽  
Biogenesis Of Mitochondria

Background One reason for the development of insulin resistance is the chronic inflammation in obesity. Materials & Methods Scientific articles in the field of knowledge on the involvement of mitochondria and mitochondrial DNA (mtDNA) in obesity and type 2 diabetes were analyzed. Results Oxidative stress developed during obesity contributes to the formation of peroxynitrite, which causes cytochrome C-related damage in the mitochondrial electron transfer chain and increases the production of reactive oxygen species (ROS), which is associated with the development of type 2 diabetes. Oxidative stress contributes to the nuclease activity of the mitochondrial matrix, which leads to the accumulation of cleaved fragments and an increase in heteroplasmy. Mitochondrial dysfunction and mtDNA variations during insulin resistance may be connected with a change in ATP levels, generation of ROS, mitochondrial division/fusion and mitophagy. This review discusses the main role of mitochondria in the development of insulin resistance, which leads to pathological processes in insulin-dependent tissues, and considers potential therapeutic directions based on the modulation of mitochondrial biogenesis. In this regard, the development of drugs aimed at the regulation of these processes is gaining attention. Conclusion Changes in the mtDNA copy number can help to protect mitochondria from severe damage during conditions of increased oxidative stress. Mitochondrial proteome studies are conducted to search for potential therapeutic targets. The use of mitochondrial peptides encoded by mtDNA also represents a promising new approach to therapy.

scholarly journals Ethanol Extract of Leaves of Cassia siamea Lam Protects against Diabetes-Induced Insulin Resistance, Hepatic, and Endothelial Dysfunctions in ob/ob Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Camille Koffi ◽  
Raffaella Soleti ◽  
Mathieu Nitiema ◽  
Patricia Mallegol ◽  
Gregory Hilairet ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
Blood Glucose ◽  
Endothelial Dysfunction ◽  
Obese Mice ◽  
Cassia Siamea ◽  
Insulin Dependent

Despite long traditional utilization and some reports on the antihyperglycemic and antihyperlipidemic action of Cassia siamea, the mechanisms involved have not been investigated yet. Thus, the objective of the present study was to investigate whether and how oral administration of the ethanolic extract of Cassia siamea Lam leaves (LECS) improves glucose and insulin homoeostasis, liver damage, and endothelial dysfunction in an experimental model of type 2 diabetes, the leptin-deficient ob/ob mice. Oxidative stress and protein expression of insulin-dependent and insulin -independent signaling pathways were studied. Obese (ob/ob) vs. control (ob/+) mice were treated daily with intragastric administration of either vehicle or LECS (200 mg/kg, per day) for 4 weeks. Fasting blood glucose, body weight, food intake, glucose and insulin tolerance, oxidative stress, and liver damage as well as vascular complications with respect to endothelial dysfunction were examined. Administration of LECS in obese mice significantly reduced blood glucose and insulin levels, improved glucose tolerance and insulin sensitivity, and restored the increase of circulating AST and ALT without modification of body weight and food intake. These effects were associated with increased activity of both insulin and AMPK pathways in the liver and skeletal muscles. Of particular interest, administration of LECS in obese mice completely prevented the endothelial dysfunction resulting from an increased NO⋅ and decreased reactive oxygen species (ROS) production in the aorta. Altogether, oral administration of LECS remarkably attenuates features of type 2 diabetes on glucose, hepatic inflammation, insulin resistance, endothelial function, and vascular oxidative stress, being as most of these effects are related to insulin-dependent and insulin-independent mechanisms. Therefore, this study points for the therapeutic potential of Cassia siamea in correcting both metabolic and vascular alterations linked to type 2 diabetes.

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 Probiotics, prebiotics, synbiotics and insulin sensitivity

2017 ◽  
Vol 31 (1) ◽  
pp. 35-51 ◽  
Author(s):  
Y. A. Kim ◽  
J. B. Keogh ◽  
P. M. Clifton
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Intestinal Permeability ◽  
Peptide Yy ◽  
Glucagon Secretion ◽  
Energy Harvest ◽  
Improve Insulin Sensitivity

AbstractAnimal studies indicate that the composition of gut microbiota may be involved in the progression of insulin resistance to type 2 diabetes. Probiotics and/or prebiotics could be a promising approach to improve insulin sensitivity by favourably modifying the composition of the gut microbial community, reducing intestinal endotoxin concentrations and decreasing energy harvest. The aim of the present review was to investigate the effects of probiotics, prebiotics and synbiotics (a combination of probiotics and prebiotics) on insulin resistance in human clinical trials and to discuss the potential mechanisms whereby probiotics and prebiotics improve glucose metabolism. The anti-diabetic effects of probiotics include reducing pro-inflammatory cytokines via a NF-κB pathway, reduced intestinal permeability, and lowered oxidative stress. SCFA play a key role in glucose homeostasis through multiple potential mechanisms of action. Activation of G-protein-coupled receptors on L-cells by SCFA promotes the release of glucagon-like peptide-1 and peptide YY resulting in increased insulin and decreased glucagon secretion, and suppressed appetite. SCFA can decrease intestinal permeability and decrease circulating endotoxins, lowering inflammation and oxidative stress. SCFA may also have anti-lipolytic activities in adipocytes and improve insulin sensitivity via GLUT4 through the up-regulation of 5'-AMP-activated protein kinase signalling in muscle and liver tissues. Resistant starch and synbiotics appear to have favourable anti-diabetic effects. However, there are few human interventions. Further well-designed human clinical studies are required to develop recommendations for the prevention of type 2 diabetes with pro- and prebiotics.

scholarly journals Beneficial Effects of Poplar Buds on Hyperglycemia, Dyslipidemia, Oxidative Stress, and Inflammation in Streptozotocin-Induced Type-2 Diabetes

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Shiqin Peng ◽  
Ping Wei ◽  
Qun Lu ◽  
Rui Liu ◽  
Yue Ding ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Crude Extract ◽  
Liver Homogenate ◽  
Control Group ◽  
Diabetic Mice ◽  
Model Control

The effects of propolis on blood glucose regulation and the alleviation of various complications caused by diabetes have been widely studied. The main source of propolis in the northern temperate zone is poplar buds. However, there is limited research on the antidiabetic activity of poplar buds. In order to evaluate the effect of poplar buds on type-2 diabetes, crude extract and 50% fraction of poplar buds were used to feed streptozotocin-induced type-2 diabetic mice. The results showed that 50% fraction could increase insulin sensitivity and reduce insulin resistance, as well as decrease the levels of fasting blood glucose, glycated hemoglobin, and glycosylated serum proteins in diabetic mice. Compared with the model control group, the 50% fraction-treated group showed significant decreases of malondialdehyde (MDA) and increases of superoxide dismutase (SOD) in serum and liver homogenate. Moreover, 50% fraction could significantly decrease total cholesterol (TC), alleviate abnormal lipid metabolism, and enhance antioxidant capacity in the serum. For inflammatory factors, feeding of 50% fraction could also reduce the levels of interleukin 6 (IL-6), tumor necrosis factorα(TNF-α), monocyte chemotactic protein 1 (MCP-1), and cyclooxygenase-2 (COX-2) in liver homogenate. Taken together, our results suggest that crude extract and 50% fraction of poplar buds, particularly the latter, can decrease blood glucose levels and insulin resistance, and 50% fraction can significantly relieve dyslipidemia, oxidative stress, and inflammation caused by type-2 diabetes.

scholarly journals Relationships With Type 2 Diabetes Mellitus of the Basic Parameters of Urine Acid Metabolism With Indicators of Insulin Resistance

2020 ◽  
Vol 6 (1) ◽  
pp. 122-128
Author(s):  
I. Madyanov
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Acid Metabolism ◽  
Density Lipoprotein ◽  
Tyg Index ◽  
Insulin Dependent

Hyperuricemia (HU) occurs in one third of patients with type 2 diabetes mellitus (DM 2). The formation of HU in DM 2 is due to metabolic factors and impaired renal function. At the stage of prediabetes, GU reveals a connection with insulin resistance (IR), it is not clear to what extent this phenomenon is associated with an increase in uricemia in DM 2. Direct assessment of IR in patients with DM 2 is difficult. There are methods for indirect estimation of IR based on the calculation of indices using the results of simple laboratory tests. These indices are based on the determination of fasting plasma levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL-C) — TG/HDL-C, TG and glucose — TyG index, as well as TG, HDL-C and glucose — MI (metabolic index). The aim of the study was to study the relationship in patients DM 2 between the main indicators of uric acid metabolism and the TG/HDL-C index, TyG index, and MI. 368 patients with DM 2 an average age of 55.8 years, and an average disease duration of 7.2 years were examined. There were 147 men, 221 women. The connection of uricemia with TG/HDL-C was established (Rs=0.2, p=0.03). In the non-insulin-dependent course of DM 2, uricemia was positively correlated with TG/HDL-C (Rs=0.21, p=0.03), negative relations of renal clearance of urates with TG/HDL-C (Rs=0.34, p=0.007) and fractional clearance of urates with TyG (Rs =−0.27, p=0.007) were recorded. In the insulin-dependent course of DM 2, a positive association of TyG with uricuria (Rs=0.44, p=0.03) and a negative correlation with GGFRT, the main enzyme for purine reuse (Rs=−0.44, p=0.03), were revealed. The results obtained do not contradict the previously established patterns of uric acid metabolism in DM 2. The conclusion is made on the feasibility of using the TG/HDL-C index as an indicator of metabolic disorders of uric acid and IR in DM 2. In the insulin-dependent course of DM2, TyG index becomes important, an increase in which is associated with increased catabolism of purines and their insufficient reutilization.

Effects of Pterostilbene on Diabetes, Liver Steatosis and Serum Lipids

2020 ◽  
Vol 28 (2) ◽  
pp. 238-252 ◽  
Author(s):  
Saioa Gómez-Zorita ◽  
Iñaki Milton-Laskíbar ◽  
Leixuri Aguirre ◽  
Alfredo Fernández-Quintela ◽  
Jianbo Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
Animal Models ◽  
Phenolic Compound ◽  
Liver Steatosis ◽  
Positive Effects

: Pterostilbene, a phenolic compound derived from resveratrol, possesses greater bioavailability than its parent compound due to the presence of two methoxyl groups. In this review, the beneficial effects of pterostilbene on diabetes, liver steatosis and dyslipidemia are summarized. Pterostilbene is a useful bioactive compound in preventing type 1 diabetes, insulin resistance and type 2 diabetes in animal models. Concerning type 1 diabetes, the main mechanisms described to justify the positive effects of this phenolic compound are increased liver glycogen content and hepatic glucokinase and phosphofructokinase activities, the recovery of pancreatic islet architecture, cytoprotection and a decrease in serum and pancreatic pro-inflammatory cytokines. As for type 2 diabetes, increased liver glucokinase and glucose-6-phosphatase and decreased fructose-1,6-biphosphatase activities are reported. When insulin resistance is induced by diets, a greater activation of insulin signaling cascade has been reported, increased cardiotrophin-1 levels and liver glucokinase and glucose- 6-phosphatase activities, and a decreased fructose-1,6-biphosphatase activity. Data concerning pterostilbene and liver steatosis are scarce so far, but the reduction in oxidative stress induced by pterostilbene may be involved since oxidative stress is related to the progression of steatosis to steatohepatitis. Finally, pterostilbene effectively reduces total cholesterol, LDL-cholesterol and serum triglyceride levels, while increases HDL-cholesterol in animal models of dyslipidemia.

The molecular link between oxidative stress, insulin resistance, and type 2 diabetes: A target for new therapies against cardiovascular diseases

2022 ◽  
Vol 62 ◽  
pp. 85-96
Author(s):  
Aikaterini Andreadi ◽  
Alfonso Bellia ◽  
Nicola Di Daniele ◽  
Marco Meloni ◽  
Renato Lauro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Diseases ◽  
New Therapies
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