Metformin: update on mechanisms of action and repurposing potential

Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(8), С. 460 - 476

Опубликована: Май 2, 2023

Язык: Английский

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Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Апрель 21, 2023

The prevalence of obesity and diabetes mellitus (DM) has been consistently increasing worldwide. Sharing powerful genetic environmental features in their pathogenesis, amplifies the impact susceptibility factors on DM. ectopic expansion adipose tissue excessive accumulation certain nutrients metabolites sabotage metabolic balance via insulin resistance, dysfunctional autophagy, microbiome-gut-brain axis, further exacerbating dysregulation immunometabolism through low-grade systemic inflammation, leading to an accelerated loss functional β-cells gradual elevation blood glucose. Given these intricate connections, most available treatments type 2 DM (T2DM) have a mutual effect each other. For example, anti-obesity drugs can be anti-diabetic some extent, medicines, contrast, shown increase body weight, such as insulin. Meanwhile, surgical procedures, especially bariatric surgery, are more effective for both T2DM. Besides guaranteeing availability accessibility all diagnostic therapeutic tools, clinical experimental investigations pathogenesis two diseases warranted improve efficacy safety newly developed treatments.

Язык: Английский

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Pathophysiology of obesity and its associated diseases

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 13(6), С. 2403 - 2424

Опубликована: Янв. 13, 2023

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that strongly contributes to development cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on public health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia formation visceral fat in non-adipose tissues evoke disease, diseases. Adipose tissue can also secrete adipokines inflammatory cytokines affect local microenvironment, induce insulin resistance, hyperglycemia, activate associated signaling pathways. This further exacerbates progression obesity-associated Although some progress treatment been achieved preclinical clinical studies, pathogenesis obesity-induced are complex unclear. We still need understand their links better guide In this review, we review between with view improve future management its co-morbidities.

Язык: Английский

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Signaling pathways and targeted therapies for psoriasis

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Язык: Английский

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Excess body weight: Novel insights into its roles in obesity comorbidities

Seminars in Cancer Biology, Год журнала: 2023, Номер 92, С. 16 - 27

Опубликована: Март 24, 2023

Excess body weight is a global health problem due to sedentary lifestyle and unhealthy diet, affecting 2 billion population worldwide. Obesity major risk factor for metabolic diseases. Notably, the of obesity largely depends on distribution, which visceral adipose tissues but not subcutaneous fats are closely associated with comorbidities, including type diabetes, non-alcoholic fatty liver disease, cardiovascular disease certain types cancer. Latest multi-omics mechanistical studies reported crucial involvement genetic epigenetic alterations, adipokines dysregulation, immunity changes, imbalance white brown tissues, gut microbial dysbiosis in mediating pathogenic association between comorbidities. In this review, we explore epidemiology excess up-to-date mechanism how lead chronic complications. We also examine utilization fat measurement as an accurate clinical parameter assessment healthy individuals outcome prediction obese subjects. addition, current approaches prevention treatment its related comorbidities further discussed.

Язык: Английский

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Pancreatic β-cell dysfunction in type 2 diabetes: Implications of inflammation and oxidative stress

World Journal of Diabetes, Год журнала: 2023, Номер 14(3), С. 130 - 146

Опубликована: Март 15, 2023

Insulin resistance and pancreatic β-cell dysfunction are major pathological mechanisms implicated in the development progression of type 2 diabetes (T2D). Beyond detrimental effects insulin resistance, inflammation oxidative stress have emerged as critical features T2D that define dysfunction. Predominant markers such C-reactive protein, tumor necrosis factor alpha, interleukin-1β consistently associated with failure preclinical models people T2D. Similarly, important stress, increased reactive oxygen species depleted intracellular antioxidants, consistent damage conditions Such illustrate a relationship between an abnormal inflammatory response generation during The current review explores clinical research on patho-logical implications Moreover, molecular relevant biomarkers involved this process discussed to divulge link Underpinning relevance review, systematic analysis evidence from randomized controlled trials is covered, potential therapeutic some commonly used antidiabetic agents modulating makers improve function.

Язык: Английский

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

Nature Reviews Endocrinology, Год журнала: 2023, Номер 20(1), С. 27 - 49

Опубликована: Окт. 16, 2023

Язык: Английский

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Iron and the Pathophysiology of Diabetes

Annual Review of Physiology, Год журнала: 2022, Номер 85(1), С. 339 - 362

Опубликована: Сен. 22, 2022

High iron is a risk factor for type 2 diabetes mellitus (T2DM) and affects most of its cardinal features: decreased insulin secretion, resistance, increased hepatic gluconeogenesis. This true across the normal range tissue levels in pathologic overload. Because iron's central role metabolic processes (e.g., fuel oxidation) regulation hypoxia sensing), participate determining rates, gluconeogenesis, choice, action, adipocyte phenotype. The related to evident or all tissues that determine phenotypes, with adipocyte, beta cell, liver playing roles. Molecular mechanisms these effects are diverse, although there may be integrative pathways at play. Elucidating has implications not only prevention treatment, but also pathogenesis other diseases are, like T2DM, associated aging, nutrition, iron.

Язык: Английский

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The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Фев. 7, 2023

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycaemia, with absolute insulin deficiency or resistance as the main cause, and causes damage to various target organs including heart, kidney neurovascular. In terms of pathological physiological mechanisms DM, oxidative stress one leading DM an important link between its complications. Oxidative phenomenon resulting from imbalance production free radicals scavenging antioxidant systems. The site reactive oxygen species (ROS) mitochondria, which are also organelles damaged. high glucose environment, impaired electron transport chain within mitochondria leads ROS, prompts increased proton leakage altered mitochondrial membrane potential (MMP), in turn releases cytochrome c (cyt-c), apoptosis. This subsequently vicious cycle clearance body's system, transcription protein synthesis DNA (mtDNA), responsible for encoding proteins, repair systems, contributing dysfunction. paper reviews dysfunction environment induced model, looks forward providing new treatment plan based on

Язык: Английский

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The Pharmacological Efficacy of Baicalin in Inflammatory Diseases

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(11), С. 9317 - 9317

Опубликована: Май 26, 2023

Baicalin is one of the most abundant flavonoids found in dried roots Scutellaria baicalensis Georgi (SBG) belonging to genus Scutellaria. While baicalin demonstrated have anti-inflammatory, antiviral, antitumor, antibacterial, anticonvulsant, antioxidant, hepatoprotective, and neuroprotective effects, its low hydrophilicity lipophilicity limit bioavailability pharmacological functions. Therefore, an in-depth study baicalin’s pharmacokinetics contributes laying theoretical foundation for applied research disease treatment. In this view, physicochemical properties anti-inflammatory activity are summarized terms bioavailability, drug interaction, inflammatory conditions.

Язык: Английский

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