Glucose transporters in adipose tissue, liver, and skeletal muscle in metabolic health and disease

Pflügers Archiv - European Journal of Physiology, Год журнала: 2020, Номер 472(9), С. 1273 - 1298

Опубликована: Июнь 26, 2020

Abstract A family of facilitative glucose transporters (GLUTs) is involved in regulating tissue-specific uptake and metabolism the liver, skeletal muscle, adipose tissue to ensure homeostatic control blood levels. Reduced transport activity results aberrant use energy substrates associated with insulin resistance type 2 diabetes. It well established that GLUT2, main regulator hepatic hexose flux, GLUT4, workhorse insulin- contraction-stimulated are critical contributors whole-body glycemia. However, molecular mechanism how controls across membranes its relation impaired glycemic diabetes remains not sufficiently understood. An array circulating metabolites hormone-like molecules potential supplementary play roles fine-tuning flux between different organs response an altered demand.

Язык: Английский

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Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake

Comprehensive physiology, Год журнала: 2020, Номер unknown, С. 785 - 809

Опубликована: Июль 8, 2020

The skeletal muscle is the largest organ in body, by mass. It also regulator of glucose homeostasis, responsible for 80% postprandial uptake from circulation. Skeletal essential metabolism, both its role and importance exercise metabolic disease. In this article, we give an overview describing diseases that are associated with dysregulation. We focus on peripheral insulin resistance potential muscle-targeted therapeutics to combat diabetes, as well other like aging obesity. particular, outline possibilities pitfalls quest mimetics, which intended target molecular mechanisms underlying beneficial effects provide a description regulate uptake, including SNARE proteins, regulators transport into muscle. © 2020 American Physiological Society. Compr Physiol 10:785-809, 2020.

Язык: Английский

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Emerging Targets in Type 2 Diabetes and Diabetic Complications

Advanced Science, Год журнала: 2021, Номер 8(18)

Опубликована: Июль 28, 2021

Abstract Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although large drug portfolio exists to keep the levels under control, these medications are not without side effects. More importantly, once diagnosed rarely reversible. Dysfunctions in kidney, retina, cardiovascular system, neurons, liver represent common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, molecular mechanisms how type develops leads irreparable damage remain elusive. This review particularly focuses on novel targets may play role pathogenesis diabetes. Further research eventually pave way for treatment—or even prevention—of along with its complications.

Язык: Английский

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Inter-organ cross-talk in metabolic syndrome

Nature Metabolism, Год журнала: 2019, Номер 1(12), С. 1177 - 1188

Опубликована: Дек. 9, 2019

Язык: Английский

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The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia

Cell Metabolism, Год журнала: 2021, Номер 33(4), С. 758 - 780

Опубликована: Апрель 1, 2021

As the principal tissue for insulin-stimulated glucose disposal, skeletal muscle is a primary driver of whole-body glycemic control. Skeletal also uniquely responds to contraction or exercise with increased sensitivity subsequent insulin stimulation. Insulin's dominating control metabolism orchestrated by complex and highly regulated signaling cascades that elicit diverse unique effects on muscle. We discuss discoveries have led our current understanding how promotes uptake in touch upon access muscle, toward glycogen, lipid, protein metabolism. draw from human rodent studies vivo, isolated preparations, cell cultures home molecular, biophysical, structural elements mediating these responses. Finally, we offer some perspective molecular defects potentially underlie failure take up efficiently during obesity type 2 diabetes.

Язык: Английский

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Mechanisms of insulin resistance related to white, beige, and brown adipocytes

Molecular Metabolism, Год журнала: 2020, Номер 34, С. 27 - 42

Опубликована: Янв. 7, 2020

The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses the molecular cellular disruptions that contribute to syndrome. However, significant uncertainty remains mechanisms its initiation long-term maintenance. To simplify resistance analysis, review focuses unifying concept adipose tissue a central regulator systemic homeostasis by controlling liver skeletal muscle metabolism. Key aspects function related reviewed are: 1) modes which specific tissues control hepatic output disposal, 2) recently acquired understanding underlying these regulation, 3) steps pathways adversely affected obesity cause resistance. Adipocyte heterogeneity required mediate multiple tolerance. White adipocytes specialize sequestering triglycerides away from liver, muscle, limit toxicity. In contrast, brown/beige are very active directly taking up response β adrenergic signaling enhancing energy expenditure. Nonetheless, white, beige, brown all share common feature secreting factors possibly exosomes act distant homeostasis. Obesity exerts deleterious effects each adipocyte functions

Язык: Английский

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Insulin: too much of a good thing is bad

BMC Medicine, Год журнала: 2020, Номер 18(1)

Опубликована: Авг. 21, 2020

Abstract Background Insulin shares a limited physiological concentration range with other endocrine hormones. Not only too low, but also high systemic insulin levels are detrimental for body functions. Main The function and clinical relevance of usually seen in association its role maintaining glucose homeostasis. However, is an anabolic hormone which stimulates large number cellular responses. excess concentrations to the balance. Although glucoregulatory activity mitigated during hyperinsulinemia by dampening efficiency signaling (“insulin resistance”), this not case most hormonal actions insulin, including promotion protein synthesis, de novo lipogenesis, cell proliferation; inhibition lipolysis, autophagy-dependent turnover, nuclear factor E2-related factor-2 (Nrf2)-dependent antioxidative; defense mechanisms. Hence, there no general resistance selective impairment causes less uptake from blood reduced activation endothelial NO synthase (eNOS). Because largely unrestricted signaling, increases risk obesity, type 2 diabetes, cardiovascular disease decreases health span life expectancy. In epidemiological studies, high-dose therapy associated increased disease. Randomized controlled trials treatment did observe any effect on risk, these studied low doses up 40 IU/day. Proof causal link between elevated comes Mendelian randomization studies comparing individuals genetically or production. Conclusions prolonged concentrations, culture, argue favor lifestyle that limits circadian levels. risks may have implications regimens used diabetes.

Язык: Английский

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Structure, function and regulation of mammalian glucose transporters of the SLC2 family

Pflügers Archiv - European Journal of Physiology, Год журнала: 2020, Номер 472(9), С. 1155 - 1175

Опубликована: Июнь 26, 2020

Abstract The SLC2 genes code for a family of GLUT proteins that are part the major facilitator superfamily (MFS) membrane transporters. Crystal structures have recently revealed how unique protein fold these enables catalysis transport. 12 transmembrane spans built from replicated trimer substructure. This 4 substructures to move relative each other, and thereby alternately opening closing cleft either internal or external side membrane. physiological substrate GLUTs is usually hexose but substrates can include urate, dehydro-ascorbate myo-inositol. varied functions related their principal substrates, cell type in which expressed extent associated with subcellular compartments. Some translocate between compartments this facilitates control function over long- short-time scales. necessary regulated supply metabolites (mainly glucose) tissues. Pathophysiological abnormalities responsible for, with, clinical problems including 2 diabetes cancer range tissue disorders, tissue-specific profiles. availability crystal has facilitated search inhibitors specific be used therapeutically. Recent studies starting unravel drug targetable properties proteins.

Язык: Английский

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Metformin and Insulin Resistance: A Review of the Underlying Mechanisms behind Changes in GLUT4-Mediated Glucose Transport

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(3), С. 1264 - 1264

Опубликована: Янв. 23, 2022

Metformin is the most commonly used treatment to increase insulin sensitivity in insulin-resistant (IR) conditions such as diabetes, prediabetes, polycystic ovary syndrome, and obesity. There a well-documented correlation between glucose transporter 4 (GLUT4) expression level of IR. Therefore, observed peripheral utilization after metformin likely comes from induction GLUT4 its increased translocation plasma membrane. However, mechanisms behind this effect critical targets are still largely undefined. The present review explores evidence for crucial role changes activation signaling pathway mediators, AMPK, several posttranscriptional modifications based on previously published preclinical clinical models metformin's mode action animal human studies. Our aim provide comprehensive studies field order shed some light complex interactions action, expression, translocation, sensitivity.

Язык: Английский

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Regulation of Skeletal Muscle Glucose Transport and Glucose Metabolism by Exercise Training

Nutrients, Год журнала: 2019, Номер 11(10), С. 2432 - 2432

Опубликована: Окт. 12, 2019

Aerobic exercise training and resistance are both well-known for their ability to improve human health; especially in individuals with type 2 diabetes. However, there critical differences between these two main forms of the adaptations that they induce body may account beneficial effects. This article reviews literature highlights key gaps our current understanding effects aerobic on regulation systemic glucose homeostasis, skeletal muscle transport metabolism.

Язык: Английский

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