Altered glucose metabolism in Alzheimer's disease: Role of mitochondrial dysfunction and oxidative stress

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 193, P. 134 - 157

Published: Oct. 4, 2022

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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Inter-organ crosstalk during development and progression of type 2 diabetes mellitus

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 20(1), P. 27 - 49

Published: Oct. 16, 2023

Language: Английский

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Protective Factors and the Pathogenesis of Complications in Diabetes

Endocrine Reviews, Journal Year: 2023, Volume and Issue: 45(2), P. 227 - 252

Published: Aug. 25, 2023

Chronic complications of diabetes are due to myriad disorders numerous metabolic pathways that responsible for most the morbidity and mortality associated with disease. Traditionally, divided into those microvascular macrovascular origin. We suggest revising this antiquated classification vascular, parenchymal, hybrid (both vascular parenchymal) tissue origin, since profile ranges from involving only tissues mostly parenchymal organs. A major paradigm shift has occurred in recent years regarding pathogenesis complications, which focus shifted studies on risks interplay between risk protective factors. While factors clearly important development chronic diabetes, have established equally significant modulating severity complications. These responses may help explain differential even lack pathologies, some tissues. Nevertheless, despite growing number field, comprehensive reviews their mechanisms action not available. This review thus focused clinical, biochemical, molecular support idea endogenous factors, roles initiation progression diabetes. In addition, also aimed identify main needs field future studies.

Language: Английский

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Insulin Resistance: The Increased Risk of Cancers

Current Oncology, Journal Year: 2024, Volume and Issue: 31(2), P. 998 - 1027

Published: Feb. 13, 2024

Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction signaling to blood glucose levels. This state observed when muscle cells, adipose tissue, and liver improperly respond particular concentration insulin. resistance related increased plasma levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states in obesity type 2 diabetes mellitus. Observations cancer patients confirm that hyperinsulinemia major factor influencing obesity, diabetes, cancer. Obesity have been reported risks initiation, progression, metastasis several cancers. However, both aforementioned pathologies independently additionally increase risk. The disorders associated with poor outcomes treatment. For example, suffering from higher recurrence rates their overall survival reduced. In these associations between risk, an overview various pathogenic mechanisms play role development discussed.

Language: Английский

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Cellular and Molecular Mechanisms of Insulin Resistance

Current Tissue Microenvironment Reports, Journal Year: 2024, Volume and Issue: 5(3), P. 79 - 90

Published: Feb. 21, 2024

Abstract Purpose of Review Although the molecular mechanism insulin resistance involves multiple factors and several intrinsic extrinsic mechanisms have been identified, this comprehensive review provides key information on some core complex interactions molecules involved in signaling pathways resistance. Recent Findings Diabetes Mellitus, most common metabolic disorder, is one greatest global medical challenges at present. There has a significant increase complications associated with diabetes such as heart disorders, stroke, neuropathy, dyslipidemia, dysfunction-associated steatotic liver disease, nephropathy. This calls for immediate strategic action to combat disorder. Insulin resistance, characteristic marker type 2 condition which regulation glucose metabolism body tissues, liver, adipose tissue, skeletal muscle, becomes disrupted. It generally hyperglycemia, hyperinsulinemia, hyperlipidemia, impaired homeostasis. Summary Understanding pathophysiological critical developing new therapeutic strategies treat polygenic multifactorial condition. Impairment caused by lipotoxicity, increased adiposity, enhanced inflammatory signaling, endoplasmic reticulum stress, adipokines, mitochondrial dysfunction, free fatty acids, dysfunctional signaling.

Language: Английский

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Macrophages, Low-Grade Inflammation, Insulin Resistance and Hyperinsulinemia: A Mutual Ambiguous Relationship in the Development of Metabolic Diseases

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(15), P. 4358 - 4358

Published: July 27, 2022

Metabolic derangement with poor glycemic control accompanying overweight and obesity is associated chronic low-grade inflammation hyperinsulinemia. Macrophages, which present a very heterogeneous population of cells, play key role in the maintenance normal tissue homeostasis, but functional alterations resident macrophage pool as well newly recruited monocyte-derived macrophages are important drivers development inflammation. While metabolic dysfunction, insulin resistance damage may trigger or advance pro-inflammatory responses macrophages, itself contributes to resulting Macrophages express receptors whose downstream signaling networks share number knots pathways pattern recognition cytokine receptors, shape polarity. The shared allow enhance attenuate both anti-inflammatory responses. This supposedly physiological function be impaired by hyperinsulinemia macrophages. review discusses mutual ambiguous relationship inflammation, resistance, insulin-dependent modulation activity focus on adipose liver.

Language: Английский

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Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(23), P. 14663 - 14663

Published: Nov. 24, 2022

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Despite its incidence, poorly understood and remains underdiagnosed, female patients are diagnosed with a delay. The heterogenous nature this complex results from combined occurrence genetic, environmental, endocrine, behavioral factors. Primary clinical manifestations PCOS derived excess androgens (anovulation, polycystic morphology, lack or scanty, irregular menstrual periods, acne hirsutism), whereas secondary include multiple metabolic, cardiovascular, psychological disorders. Dietary lifestyle factors play important roles development course PCOS, which suggests strong epigenetic environmental influences. Many studies have shown association between chronic, low-grade inflammation both ovarian tissue throughout body. In vast majority patients, elevated values inflammatory markers their gene been reported. Development vicious cycle chronic state additionally stimulated by hyperinsulinemia obesity. Changes DNA methylation, histone acetylation noncoding RNA levels presented review context oxidative stress, reactive oxygen species, signaling PCOS. Epigenetic modulation androgenic activity response to also discussed.

Language: Английский

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The Activation Mechanism of the Insulin Receptor: A Structural Perspective

Annual Review of Biochemistry, Journal Year: 2023, Volume and Issue: 92(1), P. 247 - 272

Published: March 31, 2023

The insulin receptor (IR) is a type II tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling linked to many human diseases, such as diabetes cancers. resolution revolution cryo-electron microscopy has led the determination several structures with different numbers bound molecules recent years, which have tremendously improved our understanding how activated by insulin. Here, we review insulin-induced activation mechanism IR, including (a) detailed binding modes functions at site 1 2 (b) structural transitions are required for activation. We highlight other key aspects regulation discuss remaining gaps potential avenues future research.

Language: Английский

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State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer’s Disease

Aging and Disease, Journal Year: 2023, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2023

Type 2 diabetes mellitus (T2DM) is common and increasing in prevalence worldwide, with devastating public health consequences. While peripheral insulin resistance a key feature of most forms T2DM has been investigated for over century, research on brain (BIR) more recently developed, including the context non-diabetes states. Recent data support presence BIR aging brain, even states, found that may be Alzheimer’s disease (AD) contributes to cognitive impairment. Further, therapies used treat are now being AD treatment prevention, insulin. In this review, we offer definition BIR, present evidence AD; discuss expression, function, activation receptor (INSR) brain; how could develop; tools study BIR; correlates current hallmarks; regional/cellular involvement BIR. We close discussion resilience both AD, can improved better understand future avenues research. Overall, review position paper highlights as plausible therapeutic target prevention decline dementia due AD.

Language: Английский

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