scholarly journals Chronic Beta2‐Adrenergic Receptor Stimulation Improves Whole‐Body Glucose Homeostasis through Skeletal Muscle Metabolic Reprogramming

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Jaroslawna Meister ◽  
Derek Bone ◽  
Jonas Roland Knudsen ◽  
Regina Lee ◽  
Amanda Cohen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Adrenergic Receptor ◽  
Metabolic Reprogramming ◽  
Whole Body ◽  
Receptor Stimulation

scholarly journals Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Jaroslawna Meister ◽  
Derek B. J. Bone ◽  
Jonas R. Knudsen ◽  
Luiz F. Barella ◽  
Thomas J. Velenosi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Adrenergic Receptor ◽  
Molecular Mechanisms ◽  
Muscle Metabolism ◽  
Metabolic Reprogramming ◽  
Metabolic Effects ◽  
Antidiabetic Activity ◽  
Mouse Strains ◽  
Receptor Subtypes

AbstractActivation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with β2-adrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β2-adrenergic receptor agonist. Clenbuterol administration caused pronounced improvements in glucose homeostasis and prevented the metabolic deficits in mouse models of β-cell dysfunction and insulin resistance. Studies with skeletal muscle-specific mutant mice demonstrated that these metabolic improvements required activation of skeletal muscle β2-adrenergic receptors and the stimulatory G protein, Gs. Unbiased transcriptomic and metabolomic analyses showed that chronic β2-adrenergic receptor stimulation caused metabolic reprogramming of skeletal muscle characterized by enhanced glucose utilization. These findings strongly suggest that agents targeting skeletal muscle metabolism by modulating β2-adrenergic receptor-dependent signaling pathways may prove beneficial as antidiabetic drugs.

Insulin resistance: cross-talk between adipose tissue and skeletal muscle, through free fatty acids, liver X receptor, and peroxisome proliferator-activated receptor-α signaling

2013 ◽  
Vol 15 (3) ◽  
Author(s):  
Ann Louise Olson
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Homeostasis ◽  
Glucose Transporter ◽  
Control Point ◽  
Nuclear Hormone Receptor ◽  
Whole Body ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

AbstractSkeletal muscle and adipose tissue play a major role in the regulation of whole-body glucose homeostasis. Much of the coordinated regulation of whole-body glucose homeostasis results from the regulation of lipid storage and release by adipose tissue and efficient switching between glucose oxidation and fatty acid oxidation in skeletal muscle. A control point for these biochemical actions center around the regulation of the insulin responsive glucose transporter, GLUT4. This review examines the regulation of GLUT4 in adipose tissue and skeletal muscle, in the context of the steroid nuclear hormone receptor signaling.

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.

Antioxidant supplemention in the treatment of skeletal muscle insulin resistance: potential mechanisms and clinical relevance

2008 ◽  
Vol 33 (1) ◽  
pp. 21-31 ◽  
Author(s):  
David Wright ◽  
Lindsey Sutherland
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Whole Body ◽  
Antioxidant Compounds ◽  
Muscle Insulin Resistance ◽  
Beneficial Effects ◽  
Skeletal Muscle Insulin Resistance

The incidence of type 2 diabetes has increased dramatically over the past several decades and this trend is projected to continue into the foreseeable future. Skeletal muscle insulin resistance is thought to be a key development in the pathogenesis of type 2 diabetes. Given this fact, interventions that prevent or reverse impairments in skeletal muscle action can have profound effects on whole-body glucose homeostasis. Traditional approaches used in this regard include exercise, weight loss, and insulin-sensitizing drugs such as thiazolidinediones (TZDs). Although these interventions have proven effective in improving glucose homeostasis, there are adherence issues seen with lifestyle interventions and undesirable side effects have been reported with TZDs. With these points in mind, the development of alternative strategies to maintain or improve skeletal muscle insulin sensitivity is warranted. In this context, the purpose of the present review is to highlight the role of antioxidant compounds in the prevention and treatment of skeletal muscle insulin resistance. Specifically, we will briefly describe the mechanisms of insulin-stimulated skeletal muscle glucose uptake and the potential mediators of oxidative stress induced insulin resistance, highlight data suggesting that antioxidant compounds can have beneficial effects on skeletal muscle insulin action, and discuss potential mechanisms mediating this effect.

scholarly journals Plant-Derived Trans-β-Caryophyllene Boosts Glucose Metabolism and ATP Synthesis in Skeletal Muscle Cells through Cannabinoid Type 2 Receptor Stimulation

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 916
Author(s):  
Federica Geddo ◽  
Susanna Antoniotti ◽  
Giulia Querio ◽  
Iris Chiara Salaroglio ◽  
Costanzo Costamagna ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Atp Synthesis ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Whole Body ◽  
Cb2 Receptor ◽  
Receptor Stimulation

Skeletal muscle plays a pivotal role in whole-body glucose metabolism, accounting for the highest percentage of glucose uptake and utilization in healthy subjects. Impairment of these key functions occurs in several conditions including sedentary lifestyle and aging, driving toward hyperglycemia and metabolic chronic diseases. Therefore, strategies pointed to improve metabolic health by targeting skeletal muscle biochemical pathways are extremely attractive. Among them, we focused on the natural sesquiterpene and cannabinoid type 2 (CB2) receptor agonist Trans-β-caryophyllene (BCP) by analyzing its role in enhancing glucose metabolism in skeletal muscle cells. Experiments were performed on C2C12 myotubes. CB2 receptor membrane localization in myotubes was assessed by immunofluorescence. Within glucose metabolism, we evaluated glucose uptake (by the fluorescent glucose analog 2-NBDG), key enzymes of both glycolytic and oxidative pathways (by spectrophotometric assays and metabolic radiolabeling) and ATP production (by chemiluminescence-based assays). In all experiments, CB2 receptor involvement was tested with the CB2 antagonists AM630 and SR144528. Our results show that in myotubes, BCP significantly enhances glucose uptake, glycolytic and oxidative pathways, and ATP synthesis through a CB2-dependent mechanism. Giving these outcomes, CB2 receptor stimulation by BCP could represent an appealing tool to improve skeletal muscle glucose metabolism, both in physiological and pathological conditions.

scholarly journals Delivery of adiponectin gene to skeletal muscle using ultrasound targeted microbubbles improves insulin sensitivity and whole body glucose homeostasis

2013 ◽  
Vol 304 (2) ◽  
pp. E168-E175 ◽  
Author(s):  
Vivian Vu ◽  
Ying Liu ◽  
Sanjana Sen ◽  
Aimin Xu ◽  
Gary Sweeney
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
Fluorescent Protein ◽  
Systemic Circulation ◽  
Tolerance Test ◽  
Whole Body ◽  
Glucose Disposal ◽  
Adiponectin Gene ◽  
Green Fluorescent

Numerous studies have shown that adiponectin confers antidiabetic effects via both insulin-like and insulin-sensitizing actions. The majority of adiponectin in circulation is derived from adipocytes; however, other tissues such as skeletal muscle can produce adiponectin. This study was designed to investigate the functional significance of adiponectin produced by skeletal muscle. We encapsulated the adiponectin gene in lipid-coated microspheres filled with octafluoropropane gas that were injected into the systemic circulation and destroyed within the microvasculature of skeletal muscle using ultrasound. We first demonstrated safe and successful targeting of luciferase and green fluorescent protein reporter genes to skeletal muscle using this approach and then confirmed efficient overexpression of adiponectin mRNA and oligomeric protein forms. Glucose tolerance test indicated that overexpression of adiponectin in skeletal muscle was able to improve glucose intolerance induced by feeding mice a high-fat diet (HFD), and this correlated with improved skeletal muscle insulin signaling. We then performed hyperinsulinemic-euglycemic clamp studies and demonstrated that adiponectin overexpression attenuated the decreases in glucose infusion rate, glucose disposal, and increase in glucose appearance induced by HFD. Ultrasound-targeted microbubble destruction (UTMD) delivery of adiponectin to skeletal muscle also enhanced serum adiponectin levels and improved hepatic insulin sensitivity. In conclusion, our data show that UTMD efficiently delivers adiponectin to skeletal muscle and that this improves insulin sensitivity and glucose homeostasis.

scholarly journals Soya protein reverses dyslipidaemia and the altered capacity of insulin-stimulated glucose utilization in the skeletal muscle of sucrose-rich diet-fed rats

2008 ◽  
Vol 102 (1) ◽  
pp. 60-68 ◽  
Author(s):  
María E. Oliva ◽  
Adriana G. Chicco ◽  
Yolanda B. Lombardo
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Homeostasis ◽  
Glucose Utilization ◽  
Body Weight Gain ◽  
Protein Isolate ◽  
Soya Protein ◽  
Whole Body ◽  
Control Group ◽  
Soya Protein Isolate

The present study investigates the benefits of dietary intake of soya protein upon dyslipidaemia and insulin resistance in rats chronically (8 months) fed a sucrose-rich (63 %) diet (SRD). For this purpose, we analysed the effectiveness of soya protein isolate in improving or reversing these metabolic abnormalities. Wistar rats were fed a SRD for 4 months. By the end of this period, stable dyslipidaemia and insulin resistance were present in the animals. From months 4 to 8, half the animals continued with the SRD and the other half were fed a SRD in which the source of protein casein was substituted by soya. The control group received a diet in which the source of carbohydrate was maize starch. The results showed that: (1) soya protein normalized plasma TAG, cholesterol and NEFA levels in the SRD-fed rats. Moreover, the addition of soya protein reversed the hepatic steatosis. (2) Glucose homeostasis was normalized without changes in circulating insulin levels. Whole-body peripheral insulin sensitivity substantially improved. Besides, soya protein moderately decreases body weight gain limiting the accretion of visceral fat. (3) By shifting the source of dietary protein from casein to soya during the last 4 months of the feeding period it was possible to reverse both the diminished insulin-stimulated glucose oxidation and disposal in the skeletal muscle of SRD-fed rats. This study provides new data showing the beneficial effect of soya protein upon lipid and glucose homeostasis in the experimental model of dyslipidaemia and insulin resistance.

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