scholarly journals Rho GTPases—Emerging Regulators of Glucose Homeostasis and Metabolic Health

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 434 ◽  
Author(s):  
Lisbeth Liliendal Valbjørn Møller ◽  
Amira Klip ◽  
Lykke Sylow
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Metabolic Health ◽  
Future Research ◽  
Cellular Functions ◽  
Vesicle Traffic ◽  
Cytoskeleton Remodeling ◽  
Health And Disease

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important roles of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and discuss the proposed mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

scholarly journals Rho GTPases – Emerging Regulators of Glucose Homeostasis and Metabolic Health

2019 ◽  
Author(s):  
Lisbeth L.V. Møller ◽  
Amira Klip ◽  
Lykke Sylow
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Metabolic Health ◽  
Future Research ◽  
Cellular Functions ◽  
Vesicle Traffic ◽  
Cytoskeleton Remodeling ◽  
Health And Disease

Rho guanosine triphosphatases (GTPases) are key regulators in a number of cellular functions, including actin cytoskeleton remodeling and vesicle traffic. Traditionally, Rho GTPases are studied because of their function in cell migration and cancer, while their roles in metabolism are less documented. However, emerging evidence implicates Rho GTPases as regulators of processes of crucial importance for maintaining metabolic homeostasis. Thus, the time is now ripe for reviewing Rho GTPases in the context of metabolic health. Rho GTPase-mediated key processes include the release of insulin from pancreatic β-cells, glucose uptake into skeletal muscle and adipose tissue, and muscle mass regulation. Through the current review, we cast light on the important role of Rho GTPases in skeletal muscle, adipose tissue, and the pancreas and mechanisms by which Rho GTPases act to regulate glucose metabolism in health and disease. We also describe challenges and goals for future research.

scholarly journals Role of Rho GTPase Interacting Proteins in Subcellular Compartments of Podocytes

2021 ◽  
Vol 22 (7) ◽  
pp. 3656
Author(s):  
Kana Asano-Matsuda ◽  
Sajida Ibrahim ◽  
Tomoko Takano ◽  
Jun Matsuda
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Small Gtpases ◽  
The Body ◽  
Actin Dynamics ◽  
Future Research ◽  
Cellular Functions ◽  
Waste Products ◽  
Filtration Barrier ◽  
Subcellular Compartments

The first step of urine formation is the selective filtration of the plasma into the urinary space at the kidney structure called the glomerulus. The filtration barrier of the glomerulus allows blood cells and large proteins such as albumin to be retained while eliminating the waste products of the body. The filtration barrier consists of three layers: fenestrated endothelial cells, glomerular basement membrane, and podocytes. Podocytes are specialized epithelial cells featured by numerous, actin-based projections called foot processes. Proteins on the foot process membrane are connected to the well-organized intracellular actin network. The Rho family of small GTPases (Rho GTPases) act as intracellular molecular switches. They tightly regulate actin dynamics and subsequent diverse cellular functions such as adhesion, migration, and spreading. Previous studies using podocyte-specific transgenic or knockout animal models have established that Rho GTPases are crucial for the podocyte health and barrier function. However, little attention has been paid regarding subcellular locations where distinct Rho GTPases contribute to specific functions. In the current review, we discuss cellular events involving the prototypical Rho GTPases (RhoA, Rac1, and Cdc42) in podocytes, with particular focus on the subcellular compartments where the signaling events occur. We also provide our synthesized views of the current understanding and propose future research directions.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Skeletal muscle lipotoxicity in insulin resistance and type 2 diabetes: a causal mechanism or an innocent bystander?

2017 ◽  
Vol 176 (2) ◽  
pp. R67-R78 ◽  
Author(s):  
Charlotte Brøns ◽  
Louise Groth Grunnet
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cellular Localization ◽  
Future Research ◽  
Causal Mechanism ◽  
Increased Risk ◽  
Adipose Tissue Expandability

Dysfunctional adipose tissue is associated with an increased risk of developing type 2 diabetes (T2D). One characteristic of a dysfunctional adipose tissue is the reduced expandability of the subcutaneous adipose tissue leading to ectopic storage of fat in organs and/or tissues involved in the pathogenesis of T2D that can cause lipotoxicity. Accumulation of lipids in the skeletal muscle is associated with insulin resistance, but the majority of previous studies do not prove any causality. Most studies agree that it is not the intramuscular lipids per se that causes insulin resistance, but rather lipid intermediates such as diacylglycerols, fatty acyl-CoAs and ceramides and that it is the localization, composition and turnover of these intermediates that play an important role in the development of insulin resistance and T2D. Adipose tissue is a more active tissue than previously thought, and future research should thus aim at examining the exact role of lipid composition, cellular localization and the dynamics of lipid turnover on the development of insulin resistance. In addition, ectopic storage of fat has differential impact on various organs in different phenotypes at risk of developing T2D; thus, understanding how adipogenesis is regulated, the interference with metabolic outcomes and what determines the capacity of adipose tissue expandability in distinct population groups is necessary. This study is a review of the current literature on the adipose tissue expandability hypothesis and how the following ectopic lipid accumulation as a consequence of a limited adipose tissue expandability may be associated with insulin resistance in muscle and liver.

scholarly journals Rac GTPases in Human Diseases

2010 ◽  
Vol 29 (3-4) ◽  
pp. 177-187 ◽  
Author(s):  
Sung-Yun Pai ◽  
Chaekyun Kim ◽  
David A. Williams
Keyword(s):  
Rho Gtpases ◽  
Rho Gtpase ◽  
Leukocyte Adhesion ◽  
Leukocyte Adhesion Deficiency ◽  
Cellular Functions ◽  
Knock Out ◽  
Type Iv ◽  
Rac Gtpases ◽  
Pathological Conditions ◽  
Life Threatening

Rho GTPases are members of the Ras superfamily of GTPases that regulate a wide variety of cellular functions. While Rho GTPase pathways have been implicated in various pathological conditions in humans, to date coding mutations in only the hematopoietic specific GTPase,RAC2, have been found to cause a human disease, a severe phagocytic immunodeficiency characterized by life-threatening infections in infancy. Interestingly, the phenotype was predicted by a mouse knock-out ofRAC2and resembles leukocyte adhesion deficiency (LAD). Here we review Rho GTPases with a specific focus on Rac GTPases. In particular, we discuss a new understanding of the unique and overlapping roles of Rac2 in blood cells that has developed since the generation of mice deficient in Rac1, Rac2 and Rac3 proteins. We propose that Rac2 mutations leading to disease be termed LAD type IV.

scholarly journals Rho GTPase Signaling in Health and Disease: A Complex Signaling Network

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 401
Author(s):  
Cord Brakebusch
Keyword(s):  
G Proteins ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Signaling Network ◽  
Ras Superfamily ◽  
Health And Disease ◽  
Complex Signaling ◽  
Small G Proteins

Rho GTPases are a family of small G-proteins of the Ras superfamily [...]

scholarly journals Exercising for Insulin Sensitivity – Is There a Mechanistic Relationship With Quantitative Changes in Skeletal Muscle Mass?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmine Paquin ◽  
Jean-Christophe Lagacé ◽  
Martin Brochu ◽  
Isabelle J. Dionne
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Metabolic Health ◽  
Whole Body ◽  
Future Research ◽  
Level Of Evidence ◽  
Exercise Interventions ◽  
Quantitative Changes ◽  
The Impact

Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.

Adipose tissue and skeletal muscle plasticity modulates metabolic health

2008 ◽  
Vol 114 (5) ◽  
pp. 357-368 ◽  
Author(s):  
Jozef Ukropec ◽  
Barbara Ukropcova ◽  
Timea Kurdiova ◽  
Daniela Gasperikova ◽  
Iwar Klimes
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Metabolic Health ◽  
Muscle Plasticity

scholarly journals Pharmacological Modulators of Small GTPases of Rho Family in Neurodegenerative Diseases

2021 ◽  
Vol 15 ◽  
Author(s):  
William Guiler ◽  
Addison Koehler ◽  
Christi Boykin ◽  
Qun Lu
Keyword(s):  
Neurodegenerative Diseases ◽  
Therapeutic Intervention ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Therapeutic Potential ◽  
Disease Model ◽  
Small Gtpases ◽  
Small Gtpase ◽  
Cellular Functions ◽  
Pharmacological Modulators

Classical Rho GTPases, including RhoA, Rac1, and Cdc42, are members of the Ras small GTPase superfamily and play essential roles in a variety of cellular functions. Rho GTPase signaling can be turned on and off by specific GEFs and GAPs, respectively. These features empower Rho GTPases and their upstream and downstream modulators as targets for scientific research and therapeutic intervention. Specifically, significant therapeutic potential exists for targeting Rho GTPases in neurodegenerative diseases due to their widespread cellular activity and alterations in neural tissues. This study will explore the roles of Rho GTPases in neurodegenerative diseases with focus on the applications of pharmacological modulators in recent discoveries. There have been exciting developments of small molecules, nonsteroidal anti-inflammatory drugs (NSAIDs), and natural products and toxins for each classical Rho GTPase category. A brief overview of each category followed by examples in their applications will be provided. The literature on their roles in various diseases [e.g., Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), Frontotemporal dementia (FTD), and Multiple sclerosis (MS)] highlights the unique and broad implications targeting Rho GTPases for potential therapeutic intervention. Clearly, there is increasing knowledge of therapeutic promise from the discovery of pharmacological modulators of Rho GTPases for managing and treating these conditions. The progress is also accompanied by the recognition of complex Rho GTPase modulation where targeting its signaling can improve some aspects of pathogenesis while exacerbating others in the same disease model. Future directions should emphasize the importance of elucidating how different Rho GTPases work in concert and how they produce such widespread yet different cellular responses during neurodegenerative disease progression.

Triacylglycerol lipases and metabolic control: implications for health and disease

2010 ◽  
Vol 299 (2) ◽  
pp. E162-E168 ◽  
Author(s):  
Matthew J. Watt ◽  
Lawrence L. Spriet
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Disease Prevention ◽  
Integrated Control ◽  
Adipose Triglyceride Lipase ◽  
Energy Substrate ◽  
Health And Disease ◽  
Hydrolysis Of

Fatty acids derived from the hydrolysis of adipose tissue and skeletal muscle triacylglycerol (TG) are an important energy substrate at rest and during physical activity. This review outlines the identification of the new TG lipase, adipose triglyceride lipase, the current understanding of how cellular TG lipases are regulated, and the implications for understanding the integrated control of TG lipolysis. Furthermore, this review outlines recent advances that propose a “revised” role for TG lipases in cellular function, metabolic homeostasis, and disease prevention.

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