Type 2 diabetes

The Lancet, Journal Year: 2022, Volume and Issue: 400(10365), P. 1803 - 1820

Published: Nov. 1, 2022

Language: Английский

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Obesity, Diabetes, and Increased Cancer Progression

Diabetes & Metabolism Journal, Journal Year: 2021, Volume and Issue: 45(6), P. 799 - 812

Published: Nov. 23, 2021

Rates of obesity and diabetes have increased significantly over the past decades prevalence is expected to continue rise further in coming years. Many observations suggest that are associated with an risk developing several types cancers, including liver, pancreatic, endometrial, colorectal, post-menopausal breast cancer. The path towards affected by multiple factors, adipokines, inflammatory cytokines, growth hormones, insulin resistance, hyperlipidemia. metabolic abnormalities changes levels these factors potential contribute development progression cancer through regulation distinct signaling pathways. Here, we highlight cellular molecular pathways constitute links between obesity, diabetes, mortality. This includes a description existing evidence supporting obesity-driven morphological functional alternations cells adipocytes complex interactions within tumor microenvironment.

Language: Английский

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Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia

Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Journal Year: 2021, Volume and Issue: 874-875, P. 503437 - 503437

Published: Dec. 14, 2021

Language: Английский

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Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(8), P. 101129 - 101129

Published: July 21, 2023

Moderate inflammation is essential for standard wound healing. In pathological conditions, such as diabetes, protracted and refractory wounds are associated with excessive inflammation, manifested by persistent proinflammatory macrophage states. However, the mechanisms still unclear. Herein, we perform a metabolomic profile find significant phenylpyruvate accumulation in diabetic foot ulcers. Increased impairs healing augments inflammatory responses, whereas reducing via dietary phenylalanine restriction relieves uncontrolled benefits wounds. Mechanistically, ingested into macrophages scavenger receptor CD36-dependent manner, binds to PPT1, inhibits depalmitoylase activity, thus increasing palmitoylation of NLRP3 protein. found enhance protein stability, decrease lysosome degradation, promote inflammasome activation release factors, interleukin (IL)-1β, finally triggering phenotype. Our study suggests potential strategy targeting prevent

Language: Английский

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An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 16, 2023

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as potential avenue combat obesity. Although BAT is the opposite of white (WAT) which responsible for storage, shares thermogenic capacity with beige that emerges from WAT depots. This unsurprising both and display huge difference in terms their secretory profile physiological role. In obesity, content declines these tissues acquire characteristics via process called “whitening”. rarely explored its implication whether it contributes or exacerbates Emerging research demonstrated BAT/beige whitening sophisticated metabolic complication obesity linked multiple factors. The current review provides clarification on influence various factors such diet, age, genetics, thermoneutrality, chemical exposure whitening. Moreover, defects mechanisms underpin are described. Notably, can be marked by accumulation large unilocular lipid droplets, mitochondrial degeneration, collapsed capacity, virtue dysfunction, devascularization, autophagy, inflammation.

Language: Английский

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The Role of AMPK Signaling in Brown Adipose Tissue Activation

Cells, Journal Year: 2021, Volume and Issue: 10(5), P. 1122 - 1122

Published: May 6, 2021

Obesity is becoming a pandemic, and its prevalence still increasing. Considering that obesity increases the risk of developing cardiometabolic diseases, research efforts are focusing on new ways to combat obesity. Brown adipose tissue (BAT) has emerged as possible target achieve this for functional role in energy expenditure by means increasing thermogenesis. An important metabolic sensor regulator whole-body balance AMP-activated protein kinase (AMPK), metabolism evident. This review highlights mechanisms BAT activation investigates how AMPK can be used activation. We compounds other factors able activate further discuss therapeutic use Extensive shows activated number different kinases, such LKB1, CaMKK, but also small molecules, hormones, stresses. inducing adipogenesis, maintaining mitochondrial homeostasis browning white tissue. conclude that, despite encouraging results, many uncertainties should clarified before posed anti-obesity treatment via

Language: Английский

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Exercise timing influences multi-tissue metabolome and skeletal muscle proteome profiles in type 2 diabetic patients – A randomized crossover trial

Metabolism, Journal Year: 2022, Volume and Issue: 135, P. 155268 - 155268

Published: July 28, 2022

Aims/hypothesisMetabolic effects of exercise may partly depend on the time-of-day when is performed. We tested hypothesis that timing affects adaptations in multi-tissue metabolome and skeletal muscle proteome profiles men with type 2 diabetes.MethodsMen fitting inclusion (type diabetes, age 45–68 years body mass index 23–33 kg/m2) exclusion criteria (insulin treatment, smoking, concurrent systemic disease, regular training) were included a randomized crossover trial (n = 15). Participants this metabolomics proteomics analysis fully completed all sessions 8). The consisted two weeks high-intensity interval training (HIT) (three sessions/week) either morning (08:00, n 5) or afternoon (16:45, 3), two-week wash-out period, an additional HIT at opposing time. researchers not blinded to group allocation. Blood, subcutaneous adipose tissue obtained before first, after each period. Broad-spectrum, untargeted proteomic was performed muscle, metabolomic biosamples. Differential content assessed by linear regression pathway set enrichment analyses Coordinated metabolic changes across tissues identified Spearman correlation analysis.ResultsMetabolic remained stable HIT, individual metabolites proteins altered, irrespective time day which However, coordinated relevant pathways protein categories identified. Morning similarly increased plasma diacylglycerols, acyl-carnitines, sphingomyelins lysophospholipids. Acyl-carnitines central training-induced cross-talk tissues. Plasma carbohydrates, via penthose phosphate pathway, lipids decreased compared HIT. Skeletal lipoproteins higher, mitochondrial complex III abundance lower HIT.Conclusions/interpretationWe provide comprehensive responses different times diabetes. Increased circulating lipid composition common between greater degree than training. Thus, there diurnal component response clinical relevance warrants further investigation.

Language: Английский

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High-protein diet prevents fat mass increase after dieting by counteracting Lactobacillus-enhanced lipid absorption

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(12), P. 1713 - 1731

Published: Dec. 1, 2022

Language: Английский

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The pyruvate dehydrogenase complex: Life’s essential, vulnerable and druggable energy homeostat

Mitochondrion, Journal Year: 2023, Volume and Issue: 70, P. 59 - 102

Published: March 1, 2023

Language: Английский

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Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice

BMJ Open Diabetes Research & Care, Journal Year: 2023, Volume and Issue: 11(3), P. e003282 - e003282

Published: May 1, 2023

Introduction Gut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized FMT may be a potential therapeutic method for T2DM, but its precise mechanisms T2DM remains to elucidated. Research design methods Eight db/m mice were donors control mice, 16 genetically diabetic db/db equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The group was administered fresh suspension (0.2 mL/mice) daily 4 weeks. Analysis of the GM serum metabolome carried out by 16S ribosomal RNA sequencing liquid chromatogram-mass spectrometry, respectively. Effects on gut barrier pancreas assessed using protein assays, messenger RNA, immunohistology clinical indicators testing. Results results showed treatment relieves series indicators, including fasting plasma glucose, insulin oral glucose tolerance test among others. Compared non-diabetic db/db+PBS exhibited decreased abundance Ruminococaceae, Porphyromonadaceae increased Rikenellaceae Lactobacillaceae. reversed this effect microbiome. Eleven metabolites changed between groups. Correlation analysis structural changes correlated host metabolite levels. further intestinal function, reduced inflammation caused an alteration number circulating immune cells. Conclusions FMT-mediated GM, metabolites, epithelial barrier, cells play important role efficacy disease progression.

Language: Английский

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