Trends in insulin resistance: insights into mechanisms and therapeutic strategy

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Июль 6, 2022

The centenary of insulin discovery represents an important opportunity to transform diabetes from a fatal diagnosis into medically manageable chronic condition. Insulin is key peptide hormone and mediates the systemic glucose metabolism in different tissues. resistance (IR) disordered biological response for stimulation through disruption molecular pathways target Acquired conditions genetic factors have been implicated IR. Recent biochemical studies suggest that dysregulated metabolic mediators released by adipose tissue including adipokines, cytokines, chemokines, excess lipids toxic lipid metabolites promote IR other associated with several groups abnormal syndromes include obesity, diabetes, dysfunction-associated fatty liver disease (MAFLD), cardiovascular disease, polycystic ovary syndrome (PCOS), abnormalities. Although no medication specifically approved treat IR, we summarized lifestyle changes pharmacological medications used as efficient intervention improve sensitivity. Ultimately, systematic discussion complex mechanism will help identify potential new targets closely

Язык: Английский

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Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade

Nature Immunology, Год журнала: 2024, Номер 25(7), С. 1257 - 1269

Опубликована: Май 28, 2024

Язык: Английский

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Chronic low-dose REV-ERBs agonist SR9009 mitigates constant light-induced weight gain and insulin resistance via adipogenesis modulation

Biomedical Journal, Год журнала: 2025, Номер unknown, С. 100830 - 100830

Опубликована: Янв. 1, 2025

Obesity and circadian rhythm disruption are significant global health concerns, contributing to an increased risk of metabolic disorders. Both adipose tissue rhythms play critical roles in maintaining energy homeostasis, their dysfunction is closely linked obesity. This study aimed assess the effects chronic low-dose SR9009, a REV-ERB ligand, on induced by constant light exposure mice. Mice were exposed for eight weeks (LL mice), resulting body weight, insulin resistance, white fat mass, altered clock gene expression. Low-dose SR9009 (10 mg/kg daily) was administered chronically its impact these disruptions. LL mice treated with showed reduced weight gain, mass but no overall homeostasis. suppressed Bmal1 expression restored Rev-erbα Rev-erbβ brown (WAT BAT). In vitro studies using 3T3-L1 cells indicated that inhibited adipogenesis, leading further investigation vivo. ChREBP1a Srebp-1c BAT did not affect inflammatory cytokine or adipokine expression, nor it restore Fasn, Pparγ, Prom1 both WAT BAT. These findings suggest may be potential therapeutic preventing gain resistance caused disruptions, likely through adipogenesis inhibition, though other pathways remain limited at low doses.

Язык: Английский

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The Effects of Intermittent Fasting on Brain and Cognitive Function

Nutrients, Год журнала: 2021, Номер 13(9), С. 3166 - 3166

Опубликована: Сен. 10, 2021

The importance of diet and the gut-brain axis for brain health cognitive function is increasingly acknowledged. Dietary interventions are tested their potential to prevent and/or treat disorders. Intermittent fasting (IF), abstinence or strong limitation calories 12 48 h, alternated with periods regular food intake, has shown promising results on neurobiological in animal models. In this review article, we discuss benefits IF possible effects prevention progress brain-related disorders animals humans. We do so by summarizing which through metabolic, cellular, circadian mechanisms lead anatomical functional changes brain. Our shows that there no clear evidence a positive short-term effect cognition healthy subjects. Clinical studies show epilepsy, Alzheimer's disease, multiple sclerosis disease symptoms progress. Findings from Parkinson's ischemic stroke, autism spectrum disorder, mood anxiety could benefit IF. Future research should disentangle whether hold true regardless age presence obesity. Moreover, variations patterns, total caloric intake specific nutrients may be relevant components success. Longitudinal randomized clinical trials (RCTs) will provide window into long-term development diseases.

Язык: Английский

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Biological connection of circadian rhythm and insulin resistance: a review

Biological Rhythm Research, Год журнала: 2025, Номер unknown, С. 1 - 17

Опубликована: Апрель 3, 2025

Язык: Английский

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Insulin Signaling In the Heart

AJP Endocrinology and Metabolism, Год журнала: 2021, Номер unknown

Опубликована: Май 31, 2021

Insulin receptors are highly expressed in the heart and vasculature. signaling regulates cardiac growth, survival, substrate uptake, utilization mitochondrial metabolism. modulates responses to physiological pathological stressors. Altered insulin may contribute pathophysiology of ventricular remodeling failure progression. Myocardial adapts rapidly changes systemic metabolic milieu. What initially represent an adaptation protect from carbo-toxicity, amplifying risk obesity diabetes. This review article presents multiple roles physiology pathology discusses potential therapeutic consequences modulating myocardial signaling.

Язык: Английский

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Genetic risk factors for severe and fatigue dominant long COVID and commonalities with ME/CFS identified by combinatorial analysis

Journal of Translational Medicine, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 1, 2023

Long COVID is a debilitating chronic condition that has affected over 100 million people globally. It characterized by diverse array of symptoms, including fatigue, cognitive dysfunction and respiratory problems. Studies have so far largely failed to identify genetic associations, the mechanisms behind disease, or any common pathophysiology with other conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) present similar symptoms.We used combinatorial analysis approach combinations variants significantly associated development long examine biological underpinning its various symptoms. We compared two subpopulations patients from Sano Genetics' GOLD study cohort, focusing on severe dominant phenotypes. evaluated signatures previously identified in an ME/CFS population against this understand similarities disorders may be triggered prior viral infection. Finally, we also output known associations diseases, range metabolic neurological disorders, overlap pathophysiological mechanisms.Combinatorial 73 genes were highly at least one populations included analysis. Of these, 9 acute COVID-19, 14 differentially expressed transcriptomic patients. A pathway enrichment revealed pathways most mainly aligned cardiometabolic diseases. Expanded genotype suggests specific SNX9 genotypes are significant contributor risk protection infection, but gene-disease relationship context dependent mediated interactions KLF15 RYR3. Comparison uniquely Severe Fatigue Dominant differences between enriched each subgroup. The unique immune myeloid differentiation macrophage foam cells. Genes subgroup MAPK/JNK signaling. ME/CFS, several involved circadian rhythm regulation insulin regulation. Overall, 39 SNPs can linked recent patient UK Biobank. Among COVID, 42 potentially tractable for novel drug discovery approaches, 13 these already targeted drugs clinical pipelines. From example, TLR4 antagonists repurposing candidates potential protect term impairment pathology caused SARS-CoV-2. currently evaluating targets use treating and/or ME/CFS.This demonstrates power analytics stratifying heterogeneous complex diseases do not simple monogenic etiologies. These results build upon findings analyses COVID-19 expect access additional independent, larger datasets will further improve disease insights validate treatment options COVID.

Язык: Английский

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Eat, sleep, repeat – endocrine regulation of behavioural circadian rhythms

FEBS Journal, Год журнала: 2021, Номер 289(21), С. 6543 - 6558

Опубликована: Июль 6, 2021

The adaptation of organisms to a rhythmic environment is mediated by an internal timing system termed the circadian clock. In mammals, molecular clocks are found in all tissues and organs. This clock network regulates release many hormones, which turn influence some most vital behavioural functions. Sleep-wake cycles under strict control with strong hormones such as melatonin, cortisol others. Food intake, contrast, receives modulation through leptin, ghrelin, insulin orexin. A third output covered this review mating bonding behaviours, regulated rhythms steroid oxytocin. Together, these data emphasize pervasive on outputs its mediation endocrine networks.

Язык: Английский

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Epigenetics of Hepatic Insulin Resistance

Frontiers in Endocrinology, Год журнала: 2021, Номер 12

Опубликована: Май 11, 2021

Insulin resistance (IR) is largely recognized as a unifying feature that underlies metabolic dysfunction. Both lifestyle and genetic factors contribute to IR. Work from recent years has demonstrated the epigenome may constitute an interface where different signals converge promote IR gene expression programs. Here, we review current knowledge of role epigenetics in hepatic IR, focusing on roles DNA methylation histone post-translational modifications. We discuss broad epigenetic changes observed insulin resistant liver its associated pathophysiological states leverage wealth 'omics' studies performed efforts pinpointing specific loci are disrupted by these changes. envision future studies, with increased genomic resolution larger cohorts, will further identification biomarkers early onset assist development targeted interventions. Furthermore, there growing evidence suggest persistent marks be acquired over prolonged exposure disease or deleterious exposures, highlighting need for preventative medicine long-term adjustments avoid irreversible alterations expression.

Язык: Английский

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Genetic risk factors for ME/CFS identified using combinatorial analysis

Journal of Translational Medicine, Год журнала: 2022, Номер 20(1)

Опубликована: Дек. 14, 2022

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease that lacks known pathogenesis, distinctive diagnostic criteria, and effective treatment options. Understanding the genetic (and other) risk factors associated with would begin to help alleviate some of these issues for patients.

Язык: Английский

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