Tumor Necrosis Factor‐Alpha: Role in Development of Insulin Resistance and Pathogenesis of Type 2 Diabetes Mellitus

Journal of Cellular Biochemistry, Journal Year: 2017, Volume and Issue: 119(1), P. 105 - 110

Published: June 1, 2017

ABSTRACT Pathogenesis of type 2 diabetes mellitus (T2DM) and development insulin resistance are characterized by multi‐stimuli factors notably glucolipotoxicity, generation reactive oxygen species (ROS), epigenetic factors, activation various transcriptional mediated pathways along with the augmented levels pro‐inflammatory cytokines. Among cytokines, tumor necrosis factor‐alpha (TNF‐α) is one most important mediator that critically involved in pathogenesis T2DM. TNF‐α mainly produced adipocytes and/or peripheral tissues, induces tissue‐specific inflammation through involvement ROS pathways. The raised level tissues impairing signaling serine phosphorylation leads to Anti‐TNF‐α treatment strategies have been developed reduce incidence In this article, we briefly described how plays crucial role induce To block inflammatory responses blocking may be an effective strategy for J. Cell. Biochem. 119: 105–110, 2018. © 2017 Wiley Periodicals, Inc.

Language: Английский

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Obesity and dyslipidemia

Metabolism, Journal Year: 2018, Volume and Issue: 92, P. 71 - 81

Published: Nov. 14, 2018

Language: Английский

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<p>Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications</p>

Diabetes Metabolic Syndrome and Obesity, Journal Year: 2020, Volume and Issue: Volume 13, P. 3611 - 3616

Published: Oct. 1, 2020

Abstract: Obesity is a triggering factor for diabetes associated with insulin resistance. In individuals who are obese, higher amounts of non-esterified fatty acids, glycerol, hormones, and pro-inflammatory cytokines that could participate in the development resistance released by adipose tissue. Besides, endoplasmic reticulum stress, tissue hypoxia, oxidative lipodystrophy, genetic background have role However, no effective drug therapy was developed type 2 mellitus targeting these physiological factors. This might be due to lack agreement on comprehensive mechanism Therefore, this review assesses cellular components each physiologic pathophysiologic factors involved obesity resistance, may encourage further field. Keywords: obesity, insulin,

Language: Английский

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Mechanism of Generation of Oxidative Stress and Pathophysiology of Type 2 Diabetes Mellitus: How Are They Interlinked?

Journal of Cellular Biochemistry, Journal Year: 2017, Volume and Issue: 118(11), P. 3577 - 3585

Published: May 1, 2017

ABSTRACT Oxidative stress has been considered as a major hallmark for the pathogenesis and development of type 2 diabetes mellitus (T2DM), but still it is debatable whether mere aggregation inflammatory‐induced responses or clinical entity that underlies with various pathophysiological factors. In this regard, latest studies have shown increasing trends involvement reactive oxygen species (ROS) oxidative in T2DM. ROS are highly almost all cellular components chemically changed due to influence ultimately results production lipid peroxidation. Lipid peroxidation causative factor leads overt T2DM its associated micro‐ macro‐vascular complications. article, we briefly described role factors, transcriptional metabolic pathways which responsible increase stress, most pivotal Therefore, conclude measurement biomarkers may be one optional tool diagnosis prediction Moreover, key findings article also provides new conceptual framework forthcoming investigations on drug discovery. J. Cell. Biochem. 118: 3577–3585, 2017. © 2017 Wiley Periodicals, Inc.

Language: Английский

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Health benefits of resveratrol: Evidence from clinical studies

Medicinal Research Reviews, Journal Year: 2019, Volume and Issue: 39(5), P. 1851 - 1891

Published: Feb. 11, 2019

Resveratrol is a polyphenolic nutraceutical that exhibits pleiotropic activities in human subjects. The efficacy, safety, and pharmacokinetics of resveratrol have been documented over 244 clinical trials, with an additional 27 trials currently ongoing. Resveretrol reported to potentially improve the therapeutic outcome patients suffering from diabetes mellitus, obesity, colorectal cancer, breast multiple myeloma, metabolic syndrome, hypertension, Alzheimer's disease, stroke, cardiovascular diseases, kidney inflammatory rhinopharyngitis. polyphenol be safe at doses up 5 g/d, when used either alone or as combination therapy. molecular basis for are based on its ability modulate cell signaling molecules such cytokines, caspases, matrix metalloproteinases, Wnt, nuclear factor-κB, Notch, 5'-AMP-activated protein kinase, intercellular adhesion molecule, vascular sirtuin type 1, peroxisome proliferator-activated receptor-γ coactivator 1α, insulin-like growth factor factor-binding 3, Ras association domain family pAkt, endothelial factor, cyclooxygenase 2, erythroid 2 like Kelch-like ECH-associated 1. Although utility well documented, rapid metabolism poor bioavailability limited use. In this regard, recently produced micronized formulation called SRT501, shows promise. This review discusses available data prevention, management, treatment various diseases disorders. Based current evidence, potential molecule clinic discussed.

Language: Английский

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Chronic Low Grade Inflammation in Pathogenesis of PCOS

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(7), P. 3789 - 3789

Published: April 6, 2021

Polycystic ovary syndrome (PCOS) is a one of the most common endocrine disorders, with prevalence rate 5-10% in reproductive aged women. It's characterized by (1) chronic anovulation, (2) biochemical and/or clinical hyperandrogenism, and (3) polycystic ovarian morphology. PCOS has significant implications can lead to health problems related accumulation adipose tissue, such as obesity, insulin resistance, metabolic syndrome, type 2 diabetes. There also evidence that patients are at higher risk cardiovascular diseases, atherosclerosis, high blood pressure. Several studies have reported association between low-grade inflammation. According known data, inflammatory markers or their gene patients. Correlations been found increased levels C-reactive protein (CRP), interleukin 18 (IL-18), tumor necrosis factor (TNF-α), 6 (IL-6), white cell count (WBC), monocyte chemoattractant protein-1 (MCP-1) macrophage protein-1α (MIP-1α) women compared age- BMI-matched controls. Women present elevated AGEs RAGE (receptor for advanced glycation end products) expression. This state aggravating obesity hyperinsulinemia. describing mutual impact hyperinsulinemia state. Endothelial dysfunction may be triggered cytokines. Many factors involved oxidative stress, inflammation, thrombosis were proposed showing endothelial damage PCOS. Those include asymmetric dimethylarginine (ADMA), homocysteine, plasminogen activator inhibitor-I (PAI-I), PAI-I activity, vascular growth (VEGF) etc. It was uterine hyperinflammatory responsible pregnancy complications ranging from miscarriage placental insufficiency. In this review, we discuss importance concerning role process inflammation pathogenesis

Language: Английский

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Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review

Oxidative Medicine and Cellular Longevity, Journal Year: 2020, Volume and Issue: 2020, P. 1 - 36

Published: Feb. 14, 2020

Diabetes mellitus is a metabolic disorder that majorly affects the endocrine gland, and it symbolized by hyperglycemia glucose intolerance owing to deficient insulin secretory responses beta cell dysfunction. This ailment as many 451 million people worldwide, also one of leading causes death. In spite immense advances made in development orthodox antidiabetic drugs, these drugs are often considered not successful for management treatment T2DM due myriad side effects associated with them. Thus, exploration medicinal herbs natural products therapeutic sources promoted because they have little or no effects. Bioactive molecules isolated from been proven lower blood levels via regulating more following mechanisms: improvement function, resistance, (re)absorption, glucagon-like peptide-1 homeostasis. recent times, mechanisms action different bioactive properties phytochemistry gaining lot attention area drug discovery. review article presents an update findings clinical research into plant therapy T2DM.

Language: Английский

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Effects of Magnesium Deficiency on Mechanisms of Insulin Resistance in Type 2 Diabetes: Focusing on the Processes of Insulin Secretion and Signaling

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(6), P. 1351 - 1351

Published: March 18, 2019

Magnesium (Mg2+) is an essential mineral for human health and plays important role in the regulation of glucose homeostasis insulin actions. Despite widespread clinical evidences association Mg2+ deficiency (MgD) type 2 diabetes mellitus (T2D), molecular mechanisms by which contributes to resistance (IR) are still under discussion. regulates electrical activity secretion pancreatic beta-cells. Intracellular concentrations critical phosphorylation receptor other downstream signal kinases target cells. Low levels result a defective tyrosine kinase activity, post-receptor impairment action, altered cellular transport, decreased utilization, promotes peripheral IR T2D. MgD triggers chronic systemic inflammation that also potentiates IR. People with T2D may end up vicious circle increases causes MgD, requires periodic monitoring serum levels.

Language: Английский

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Obesity and Breast Cancer: A Paradoxical and Controversial Relationship Influenced by Menopausal Status

Frontiers in Oncology, Journal Year: 2021, Volume and Issue: 11

Published: Aug. 13, 2021

Breast cancer is the most common tumor in women worldwide, and an increasing public health concern. Knowledge of both protective negative risk factors essential for a better understanding this heterogenous disease. We undertook review recent literature evaluated relationship between obesity mediators breast development depending on menopausal status. Excess weight now pandemic has replaced tobacco as main lifestyle-related factor premature death. Although prevalence obesity/overweight increased globally over last 50 years, potential harm attributable to excess fat generally been underestimated. The overweight/obesity, overall appears be highly dependent Thus, increases postmenopausal but, conversely, it premenopausal women. evaluate role different clinical potentially involved seemingly contradictory relationship, including estrogen, mammogram density, adipokines, insulin-signaling pathway activation, inflammatory A key focus understand impact body mass index status these and, hence, provide some clarity into inter-relationships controversial issue.

Language: Английский

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Pancreatic endocrine and exocrine signaling and crosstalk in physiological and pathological status

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 13, 2025

Abstract The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion exocrine digestive enzymes. Complex interactions signaling mechanisms between functions of pancreas play a crucial role in maintaining metabolic homeostasis overall health. Compelling evidence indicates direct indirect crosstalk parts, influencing development diseases affecting both. From developmental perspective, parts share same origin—the “tip-trunk” domain. In certain circumstances, pancreatic cells may transdifferentiate into endocrine-like cells, insulin-secreting cells. Additionally, several diseases, including cancer, pancreatitis, diabetes, exhibit potential relevance to both functions. Endocrine communicate directly cytokines or indirectly regulating immune microenvironment. This affects onset progression these diseases. review summarizes history milestones findings related their embryonic development, phenotypic transformations, roles health disease, endocrine-exocrine from perspective therapeutic targets. Elucidating regulatory provide novel insights for understanding treatment

Language: Английский

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