Advances in Research on Type 2 Diabetes Mellitus Targets and Therapeutic Agents

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13381 - 13381

Published: Aug. 29, 2023

Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong terminal stage disease, i.e., type 2 diabetes (T2DM). The World Health Organization predicts that will be seventh leading cause death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists SGLT-2 inhibitors, single-target drugs are gradually failing to meet therapeutic requirements owing individual variability, diversity pathogenesis, organismal resistance. Therefore, there remains need investigate pathogenesis T2DM more depth, identify targets, provide improved glycemic control solutions. This review presents an overview mechanisms action development latest agents targeting years. It also discusses emerging target-based therapies new targets emerged within last three aim our theoretical basis for further advancement targeted T2DM.

Language: Английский

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On the limits of 16S rRNA gene-based metagenome prediction and functional profiling

Microbial Genomics, Journal Year: 2024, Volume and Issue: 10(2)

Published: Feb. 29, 2024

Molecular profiling techniques such as metagenomics, metatranscriptomics or metabolomics offer important insights into the functional diversity of microbiome. In contrast, 16S rRNA gene sequencing, a widespread and cost-effective technique to measure microbial diversity, only allows for indirect estimation function. To mitigate this, tools PICRUSt2, Tax4Fun2, PanFP MetGEM infer profiles from sequencing data using different algorithms. Prior studies have cast doubts on quality these predictions, motivating us systematically evaluate matched metagenomic datasets, simulated data. Our contribution is threefold: (i) data, we investigate if technical biases could explain discordance between inferred expected results; (ii) considering human cohorts type two diabetes, colorectal cancer obesity, test health-related differential abundance measures categories are concordant gene-inferred metagenome-derived and; (iii) since copy number an confounder in inference, customised normalisation with rrnDB database improve results. results show that gene-based inference generally do not necessary sensitivity delineate changes microbiome should thus be used care. Furthermore, outline differences individual tested recommendations tool selection.

Language: Английский

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Plasma metabolic profiles predict future dementia and dementia subtypes: a prospective analysis of 274,160 participants

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: Jan. 22, 2024

Abstract Background Blood-based biomarkers for dementia are gaining attention due to their non-invasive nature and feasibility in regular healthcare settings. Here, we explored the associations between 249 metabolites with all-cause (ACD), Alzheimer’s disease (AD), vascular (VaD) assessed predictive potential. Methods This study included 274,160 participants from UK Biobank. Cox proportional hazard models were employed investigate longitudinal dementia. The importance of these was quantified using machine learning algorithms, a metabolic risk score (MetRS) subsequently developed each type. We further investigated how MetRS stratified onset its performance, both alone combination demographic cognitive predictors. Results During median follow-up 14.01 years, 5274 Of examined, 143 significantly associated incident ACD, 130 AD, 140 VaD. Among dementia, lipoprotein lipid concentrations, linoleic acid, sphingomyelin, glucose, branched-chain amino acids ranked top importance. Individuals within tertile faced greater developing than those lowest tertile. When combined predictors, model yielded area under receiver operating characteristic curve (AUC) values 0.857 0.861 0.873 Conclusions conducted largest metabolome investigation date, first time revealed metabolite ranking, highlighted contribution plasma prediction.

Language: Английский

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PPM1K-regulated impaired catabolism of branched-chain amino acids orchestrates polycystic ovary syndrome

EBioMedicine, Journal Year: 2023, Volume and Issue: 89, P. 104492 - 104492

Published: March 1, 2023

Language: Английский

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Amino Acid Catabolism: An Overlooked Area of Metabolism

Nutrients, Journal Year: 2023, Volume and Issue: 15(15), P. 3378 - 3378

Published: July 29, 2023

Amino acids have been extensively studied in nutrition, mainly as key elements for maintaining optimal protein synthesis the body well precursors of various nitrogen-containing compounds. However, it is now known that amino acid catabolism an important element metabolic control different biological processes, although still a developing field to deeper understanding its implications. The mechanisms involved regulation include contribution gut microbiota oxidation and metabolite generation intestine, molecular transcriptional control, participation specific miRNAs degrading enzymes. In addition, molecules derived from play role metabolism they are used epigenetic many genes. Thus, this review aims examine support idea process associated with immune response, abnormalities during obesity, particular insulin resistance, thermogenesis.

Language: Английский

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Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus

Nutrients, Journal Year: 2023, Volume and Issue: 15(21), P. 4671 - 4671

Published: Nov. 4, 2023

Insulin resistance is an important feature of metabolic syndrome and a precursor type 2 diabetes mellitus (T2DM). Overnutrition-induced obesity major risk factor for the development insulin T2DM. The intake macronutrients plays key role in maintaining energy balance. components distinctly regulate sensitivity glucose homeostasis. Precisely adjusting beneficial food compound prevention Here, we reviewed effects different on their underlying mechanisms, including fructose, dietary fiber, saturated unsaturated fatty acids, amino acids. Understanding diet-gene interaction will help us to better uncover molecular mechanisms T2DM promote application precision nutrition practice by integrating multi-omics analysis.

Language: Английский

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Protein lipoylation: mitochondria, cuproptosis, and beyond

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(8), P. 729 - 744

Published: May 6, 2024

Language: Английский

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Dissecting mechanisms of fecal microbiota transplantation efficacy in disease

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(3), P. 209 - 222

Published: Jan. 8, 2024

Language: Английский

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Decoding the nexus: branched-chain amino acids and their connection with sleep, circadian rhythms, and cardiometabolic health

Neural Regeneration Research, Journal Year: 2024, Volume and Issue: 20(5), P. 1350 - 1363

Published: June 3, 2024

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and, either directly or indirectly, overall body health, encompassing metabolic and cardiovascular well-being. Given the heightened activity of brain, there exists a considerable demand nutrients in comparison to other organs. Among these, branched-chain amino acids, comprising leucine, isoleucine, valine, display distinctive significance, from their contribution protein structure involvement metabolism, especially cerebral processes. first acids that are released into circulation post-food intake, assume pivotal role regulation synthesis, modulating insulin secretion acid sensing pathway target rapamycin. Branched-chain key players influencing brain’s uptake monoamine precursors, competing shared transporter. Beyond these contribute cycles γ-aminobutyric glutamate, well energy metabolism. Notably, they impact GABAergic neurons excitation/inhibition balance. rhythmicity plasma concentrations, observed over 24-hour conserved rodent models, is under circadian clock control. mechanisms underlying those rhythms physiological consequences disruption not fully understood. Disturbed sleep, obesity, diabetes, diseases can elevate concentrations modify oscillatory dynamics. driving effects currently focal point ongoing research efforts, since normalizing levels has ability alleviate severity pathologies. In this context, Drosophila model, though underutilized, holds promise shedding new light on mechanisms. Initial findings indicate its potential introduce novel concepts, particularly elucidating intricate connections between clock, sleep/wake, Consequently, use transport emerge critical components orchestrators web interactions across multiple organs throughout sleep/wake cycle. They could represent one so far elusive connecting sleep patterns paving way therapeutic interventions.

Language: Английский

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Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity

Nature Cancer, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

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