MicroRNAs Dependent G‐ELNs Based Intervention Improves Glucose and Fatty Acid Metabolism While Protecting Pancreatic β‐Cells in Type 2 Diabetic Mice DOI
Geetika Bajaj,

Diksha Choudhary,

Vishal Singh

et al.

Small, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 8, 2024

Abstract Metabolic disorders such as Type 2 diabetes mellitus (T2DM) imposes a significant global health burden. Plant‐derived exosome like nanoparticles (P‐ELNs) have emerged promising therapeutic alternate for various diseases. Present data demonstrates that treatment with Ginger‐derived (G‐ELNs) enhance insulin dependent glucose uptake, downregulate gluconeogenesis and oxidative stress in resistant HepG2 cells. Furthermore, oral administration of G‐ELNs T2DM mice decreases fasting blood levels improves tolerance effectively metformin. These improvements are attributed to the enhanced phosphorylation Protein kinase B (Akt‐2), phosphatidylinositol 3‐kinase at serine 474 which consequently leads increase hepatic sensitivity, improvement homeostasis decrease ectopic fat deposition. Oral also exerts protective effect on Streptozotocin (STZ)‐induced pancreatic β‐cells damage, contributing systemic amelioration T2DM. Further, per computational tools, miRNAs present modulate (PI3K)/Akt‐2 pathway exhibit strong interactions target mRNAs responsible gluconeogenesis, deposition stress. synthetic mimic miRNA downregulates its mRNA Overall, results indicate metabolism thus, exerting effects

Language: Английский

Mitochondrial Dysfunction, Oxidative Stress, and Inter-Organ Miscommunications in T2D Progression DOI Open Access
Rajakrishnan Veluthakal,

Diana Esparza,

Joseph M. Hoolachan

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1504 - 1504

Published: Jan. 25, 2024

Type 2 diabetes (T2D) is a heterogenous disease, and conventionally, peripheral insulin resistance (IR) was thought to precede islet β-cell dysfunction, promoting progression from prediabetes T2D. New evidence suggests that T2D-lean individuals experience early dysfunction without significant IR. Regardless of the primary event (i.e., IR vs. dysfunction) contributes dysglycemia, early-onset oxidative damage mitochondrial in multiple metabolic tissues may be driver T2D onset progression. Oxidative stress, defined as generation reactive oxygen species (ROS), mediated by hyperglycemia alone or combination with lipids. Physiological stress promotes inter-tissue communication, while pathological mis-communication, new this via extracellular vesicles (EVs), including mitochondria containing EVs. Under metabolic-related conditions, EV-mediated cross-talk between β-cells skeletal muscle likely trigger anomalies leading This article reviews underlying molecular mechanisms ROS-related pathogenesis prediabetes, mitophagy dynamics due stress. Further, review will describe potential various therapeutic avenues for attenuating damage, reversing preventing

Language: Английский

Citations

22
The Role of Glutathione and Its Precursors in Type 2 Diabetes DOI Creative Commons

Dawn Tuell,

George S. Ford,

Evan Los

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 184 - 184

Published: Feb. 1, 2024

Type 2 diabetes (T2D) is a major worldwide health crisis affecting about 6.2% of the world’s population. Alarmingly, one in five children USA have prediabetes. Glutathione (GSH) and its precursors play promising role prevention management type T2D. Oxidative stress (OxS) probable factor both T2D initiation progression. GSH cytosolic water-soluble chemical antioxidant emerging evidence supports improving outcomes. Dietary supplementation with N-acetyl-cysteine (NAC) and/or glycine (GLY), which are precursors, has also been studied for possible beneficial effects on This review will focus underlying pathophysiological molecular mechanisms linking OxS. In addition to their traditional roles, vivo GSH/NAC/GLY supplements be evaluated potential abilities modulate complex pro-oxidant factors (e.g., hyperglycemia) driving Positive feedback loops that amplify OxS over long time intervals likely result irreversible micro- macro-vascular damage. Most clinical studies focused adults or elderly. Future research pediatric populations should high priority since early intervention critical.

Language: Английский

Citations

11
Cuproptosis: potential new direction in diabetes research and treatment DOI Creative Commons

Jiashu Qu,

Yifan Wang,

Qiuyue Wang

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: June 5, 2024

Cuproptosis, a recently discovered form of cell death, stems from an overabundance copper ions infiltrating mitochondria. These directly engage lipoylated proteins, prompting their oligomerization and subsequent loss iron-sulfur clusters. This sequence induces proteotoxic stress, ultimately culminating in death. Type 2 diabetes, chronic metabolic disorder resulting complex interplay genetic environmental factors, has not yet been fully understood terms its etiology pathogenesis. Intricately, it is linked to various modalities including mitochondrial autophagy, apoptosis, pyroptosis, ferroptosis. Studies have impaired metabolism individuals with hinting at unique role for homeostasis the progression disease. To this end, present research aims delineate potential correlation between cuproptosis diabetes by exhaustively reviewing existing literature. By synthesizing relevant on cuproptosis, paper intends lay groundwork thorough exploration pathogenesis development targeted therapeutic interventions. The ultimate objective facilitate deeper understanding identify novel strategies associated cuproptosis.

Language: Английский

Citations

4
Maternal Serum Metabolomics in Mid-Pregnancy Identifies Lipid Pathways as a Key Link to Offspring Obesity in Early Childhood DOI Open Access
Ellen C. Francis, Katerina Kechris, Randi K. Johnson

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7620 - 7620

Published: July 11, 2024

Maternal metabolism during pregnancy shapes offspring health via in utero programming. In the Healthy Start study, we identified five subgroups of pregnant women based on conventional metabolic biomarkers: Reference (n = 360); High HDL-C 289); Dyslipidemic–High TG 149); FFA 180); Insulin Resistant (IR)–Hyperglycemic 87). These not only captured heterogeneity among participants but were also associated with obesity early childhood, even without or diabetes. Here, utilize metabolomics data to enrich characterization and identify key compounds driving between-group differences. We analyzed fasting blood samples from 1065 at 18 gestational weeks using untargeted metabolomics. used weighted gene correlation network analysis (WGCNA) derive a global subgroup characterized distinct metabolite modules representative different metabolomic profiles. mummichog algorithm for pathway enrichment that differed across subgroups. Eight representing pathways such as carnitine–acylcarnitine translocase system, fatty acid biosynthesis activation, glycerophospholipid identified. A module included 189 related DHA peroxidation, oxidative stress, sex hormone was elevated Resistant–Hyperglycemic vs. subgroup. This positively correlated total cholesterol (R:0.10; p-value < 0.0001) free acids (R:0.07; 0.05). Oxidative stress inflammatory may underlie insulin resistance pregnancy, below clinical diabetes thresholds. findings highlight potential therapeutic targets strategies risk stratification reveal mechanisms underlying developmental origins disease risk.

Language: Английский

Citations

4
Hypoxia and aging: molecular mechanisms, diseases, and therapeutic targets DOI Creative Commons
Ayesha Nisar,

Sawar Khan,

Wen Li

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(11)

Published: Oct. 15, 2024

Abstract Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, epigenetic modifications. This review explores interconnected roles hypoxia in aging, highlighting how hypoxic conditions exacerbate damage, promote senescence, contribute age‐related pathologies, including cardiovascular neurodegenerative disorders, cancer, metabolic dysfunctions, pulmonary conditions. By examining mechanisms linking we identify key serve potential therapeutic targets. Emerging interventions such HIF modulators, antioxidants, senolytics, lifestyle modifications hold promise mitigating adverse effects on tissues. However, challenges heterogeneity lack reliable biomarkers, safety concerns regarding hypoxia‐targeted therapies remain. emphasizes need for personalized approaches advanced technologies develop effective antiaging interventions. integrating current knowledge, this provides comprehensive framework underscores importance targeting hypoxia‐induced enhance healthy reduce burden diseases.

Language: Английский

Citations

4
The impact of extracellular glucose concentrations on antioxidant capacity, viability, and microRNA expression in TM4 Sertoli cells DOI
Farha A. Ali Shafi, Ali Thoulfikar Abdul Imeer,

Hassan Ali Abood Nassrullah

et al.

Reproductive Biology, Journal Year: 2025, Volume and Issue: 25(2), P. 101015 - 101015

Published: April 1, 2025

Language: Английский

Citations

0
Relationships among osteoporosis, redox homeostasis, and alcohol addiction: Importance of the brain-bone axis DOI
Monika Martiniaková, Veronika Kováčová, Roman Bíro

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 187, P. 118063 - 118063

Published: April 19, 2025

Language: Английский

Citations

0
N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3β pathway DOI Creative Commons

Yuechang Huang,

Xingmin Zhang, Qian Li

et al.

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: April 25, 2024

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic β-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects mechanisms of action N- p -coumaroyloctopamine (N-p-CO) vitro vivo . N-p-CO exhibited high antioxidant activity, indicated increased activity SOD, GSH GSH-Px HL-7702 cells induced both glucose (HG) palmitic acid (PA). treatment significantly augmented uptake glycogen synthesis HG/PA-treated cells. Moreover, administration diabetic mice high-fat diet (HFD) streptozotocin (STZ) not only levels GSH-PX, SOD GSH, but also dramatically alleviated hepatic metabolism dose-dependent manner. More importantly, upregulated expressions PI3K, AKT GSK3β proteins HG/PA-induced HFD/STZ-induced mice. These findings clearly suggest that exerts anti-oxidant effects, most probably via regulation PI3K/AKT/GSK3β signaling pathway. Thus, have potentials new candidate for prevention diabetes.

Language: Английский

Citations

2
Unveiling the Nutritional Veil of Sulforaphane: With a Major Focus on Glucose Homeostasis Modulation DOI Open Access
Yanan Wang, Xiaoyun He, Nan Cheng

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(12), P. 1877 - 1877

Published: June 14, 2024

Abnormal glucose homeostasis is associated with metabolic syndromes including cardiovascular diseases, hypertension, type 2 diabetes mellitus, and obesity, highlighting the significance of maintaining a balanced level for optimal biological function. This highlights importance normal levels proper functioning. Sulforaphane (SFN), primary bioactive compound in broccoli from Cruciferae or Brassicaceae family, has been shown to enhance effectively while exhibiting low cytotoxicity. paper assesses impact SFN on vitro, vivo, human trials, as well molecular mechanisms that drive its regulatory effects. New strategies have proposed bioavailability targeted delivery order overcome inherent instability. The manuscript also covers safety evaluations documented production utilization. Hence, deeper understanding favorable influence mechanism homeostasis, coupled fact abundant daily diet, may ultimately offer theoretical evidence support potential use food pharmaceutical industries.

Language: Английский

Citations

2
Diabetic microenvironment deteriorates the regenerative capacities of adipose mesenchymal stromal cells DOI Creative Commons
Sara M. Ahmed, Hoda Elkhenany,

Toka A. Ahmed

et al.

Diabetology & Metabolic Syndrome, Journal Year: 2024, Volume and Issue: 16(1)

Published: June 16, 2024

Abstract Background Type 2 diabetes is an endocrine disorder characterized by compromised insulin sensitivity that eventually leads to overt disease. Adipose stem cells (ASCs) showed promising potency in improving type and its complications through their immunomodulatory differentiation capabilities. However, the hyperglycaemia of diabetic microenvironment may exert a detrimental effect on functionality ASCs. Herein, we investigate ASC homeostasis regenerative potential milieu. Methods We conducted data collection functional enrichment analysis differential gene expression profile MSCs microenvironment. Next, ASCs were cultured medium containing serum (DS) or normal non-diabetic (NS) for six days one-month periods. Proteomic was carried out, then evaluated apoptosis, changes surface markers DNA repair genes, intracellular oxidative stress, capacity. The crosstalk between determined pro anti-inflammatory cytokines cytokine receptors. Results differentially expressed genes points alteration stress regulating pathways MSCs. proteomic DS revealed proteins are related enhanced cellular damage altered potential. Our experiments confirmed these suffered defective repair. Under conditions, also osteogenic, adipogenic, angiogenic capacities. Both pro- significantly culture denoting Interestingly, induction antioxidative such as SIRT1, TERF1, Clusterin PKM2. Conclusion propose this deterioration function partially mediated induced inflammatory factors indicate adaptation mechanism increased

Language: Английский

Citations

2