Exercise and insulin signaling: a historical perspective

2002 ◽  
Vol 93 (2) ◽  
pp. 765-772 ◽  
Author(s):  
Eva Tomás ◽  
Antonio Zorzano ◽  
Neil B. Ruderman
Keyword(s):  
Insulin Signaling ◽  
Historical Perspective ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
The People ◽  
Current Thinking ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
Considerable Body

Over the past 30 years, a considerable body of evidence has revealed that a prior bout of exercise can increase the ability of insulin to stimulate glucose transport and glycogen synthesis in skeletal muscle. Apart from its clinical implications, this work has led to a considerable effort to determine at a molecular level how exercise causes this effect and, in particular, whether it does so by enhancing specific events in the insulin-signaling cascade. The objective of this review is to discuss from a historical perspective how our current thinking in this area has evolved and the people responsible for it. Areas to be discussed include the effect or lack of effect of prior exercise on the insulin-signaling pathway, effects of exercise on the regulation by insulin of the GLUT-4 glucose transporter in muscle, and the emerging role of AMP-activated protein kinase as a mediator of exercise-induced signaling events. In addition, we will discuss briefly some of the avenues that research in this area is likely to follow.

Carbohydrate and Protein Supplements, an Effective Means for Maintaining Exercise-Induced Glucose Metabolism Homeostasis

2021 ◽  
Vol 11 (6) ◽  
pp. 1120-1128
Author(s):  
Dingguo Ruan ◽  
Hong Deng ◽  
Xiaoyang Xu
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Normal Saline ◽  
Glucose Transporter ◽  
Glycogen Synthesis ◽  
Effective Means ◽  
Recovery Period ◽  
Future Application ◽  
Glut 4 ◽  
Exercise Induced

This study aimed to verify the effects of an independently developed carbohydrate and protein (CHO+P) beverage (7.2% oligosaccharide and 1.6% soy-polypeptide) supplement on exerciseinduced glucose metabolism and associated gene expression. Mice received 1 mL/100 g body weight of normal saline (group C; n = 36) or CHO+P (group E; n = 36) at 30 min before an immediately after exercise. Mice without exercise and supplementation served as normal controls (group NC; n = 9). The expression levels related to glucose metabolism were measured at 0, 4, 12, and 24 h after exercise (n = 9 per group). The blood glucose, insulin, and liver glycogen contents in groups C and E were dramatically lower than group NC immediately after exercise. Those in group E were significantly higher than group C, with few differences between the two. Muscle glycogen was restored more quickly when the CHO+P beverage was consumed compared to normal saline. Furthermore, exercise-induced increase in glucose transporter-4 (GLUT-4) mRNA could be depressed by CHO+P supplementation but enhanced in GLUT-4 protein. Interleukin-6 (IL-6) showed a double peak curve in the recovery period, but IL-6 increased again in group E earlier than group C. These findings confirmed that the beverage has significantly improved time in maintaining blood glucose stability, reducing glycogen consumption, accelerating glycogen resynthesis, and repairing injury in rats. This study suggests the future application of this beverage in humans with experimental support and provides a scientific direction for promoting glycogen synthesis and recovery through nutrition.

scholarly journals Glycogenolysis in Astrocytes Supports Blood-Borne Glucose Channeling Not Glycogen-Derived Lactate Shuttling to Neurons: Evidence from Mathematical Modeling

2010 ◽  
Vol 30 (12) ◽  
pp. 1895-1904 ◽  
Author(s):  
Mauro DiNuzzo ◽  
Silvia Mangia ◽  
Bruno Maraviglia ◽  
Federico Giove
Keyword(s):  
Glycogen Synthesis ◽  
Product Inhibition ◽  
Current Thinking ◽  
Metabolic Requirement ◽  
Previous Modeling Study ◽  
Extracellular Glucose ◽  
Subcellular Domains ◽  
Glucose Phosphorylation ◽  
Flow Through

In this article, we examined theoretically the role of human cerebral glycogen in buffering the metabolic requirement of a 360-second brain stimulation, expanding our previous modeling study of neurometabolic coupling. We found that glycogen synthesis and degradation affects the relative amount of glucose taken up by neurons versus astrocytes. Under conditions of 175:115 mmol/L (∼1.5:1) neuronal versus astrocytic activation-induced Na+ influx ratio, ∼12% of astrocytic glycogen is mobilized. This results in the rapid increase of intracellular glucose-6-phosphate level on stimulation and nearly 40% mean decrease of glucose flow through hexokinase (HK) in astrocytes via product inhibition. The suppression of astrocytic glucose phosphorylation, in turn, favors the channeling of glucose from interstitium to nearby activated neurons, without a critical effect on the concurrent intercellular lactate trafficking. Under conditions of increased neuronal versus astrocytic activation-induced Na+ influx ratio to 190:65 mmol/L (∼3:1), glycogen is not significantly degraded and blood glucose is primarily taken up by neurons. These results support a role for astrocytic glycogen in preserving extracellular glucose for neuronal utilization, rather than providing lactate to neurons as is commonly accepted by the current ‘thinking paradigm’. This might be critical in subcellular domains during functional conditions associated with fast energetic demands.

scholarly journals Insulin Signaling Attenuates GLUT4 Endocytosis in Muscle Cells via GSK3α-Dyn2-Bin1 Interplay

2021 ◽  
Author(s):  
Jessica Laiman ◽  
Julie Loh ◽  
Wei-Chun Tang ◽  
Mei-Chun Chuang ◽  
Bi-Chang Chen ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Glucose Transporter ◽  
Muscle Cells ◽  
Postprandial Glucose ◽  
Muscle Physiology ◽  
Centronuclear Myopathy ◽  
Glucose Transporter 4 ◽  
Membrane Fission ◽  
Dynamin 2

AbstractInsulin-induced translocation of glucose transporter 4 (GLUT4) to the plasma membrane of skeletal muscle is critical for postprandial glucose uptake; however, whether the internalization of GLUT4 into cells is also regulated by insulin signaling remains unclear. Here, we discover that the activity of dynamin-2 (Dyn2), pivotal GTPase catalyzing GLUT4 internalization, is regulated by insulin signaling in muscle cells. The membrane fission activity of Dyn2 is inhibited in muscle cells through binding with the SH3 domain-containing protein Bin1. Phosphorylation of Serine848 on Dyn2 by GSK3α or the mutations of Bin1-SH3 in patients with centronuclear myopathy, elevate the activity of Dyn2 due to reduced binding affinity toward Bin1. The augmented Dyn2 fission activity in muscle cells leads to GLUT4 internalization and Bin1-tubule vesiculation. Together, our findings reveal a new role of insulin signaling in glucose metabolism and muscle physiology via attenuating Dyn2 activity thus regulating GLUT4 endocytosis in muscle cell.

scholarly journals Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPKα signalling pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Mu ◽  
Huang-Guan Dai ◽  
Ling-Bo Luo ◽  
Jing Yang
Keyword(s):  
Oxidative Stress ◽  
Sperm Count ◽  
Underlying Mechanism ◽  
Signalling Pathway ◽  
Protective Effects ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase

Abstract Background Infertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis. Methods Male mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used. Results The data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro. Conclusions In conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.

scholarly journals A Socio-Historical Perspective on Ponzi Schemes and Development in Nigeria: The Role of the Christian Church

2021 ◽  
Vol 8 (2) ◽  
pp. 41
Author(s):  
Oluwasegun Peter Aluko ◽  
Ibukun Oluwakemi Olawuni
Keyword(s):  
Historical Perspective ◽  
Christian Church ◽  
Historical Approach ◽  
The People ◽  
Ponzi Scheme ◽  
The Impact

This paper is a study on Ponzi schemes, development and the Christian church in Nigeria. It traced the emergence of Ponzi schemes in Nigeria. The paper considered the practices of Mavrodi Mondial Movement (MMM), being one of the strongest Ponzi schemes in Nigeria. It assessed the impact of this Ponzi scheme on development in the country. It also looked into the role played by the Christian Church during the period of the scheme’s existence in the country. The paper, however concluded that, despite the people involved in the scheme being interested in supposedly helping people (including those in the scheme and the less privileged), it is contrary to the ethos of Christianity that touches on labour and its corresponding success. The data collected for the study were analysed using socio-historical approach.

scholarly journals The AMP-activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribonucleoside, regulates lactate production in rat Sertoli cells

2007 ◽  
Vol 39 (4) ◽  
pp. 279-288 ◽  
Author(s):  
María Noel Galardo ◽  
María Fernanda Riera ◽  
Eliana Herminia Pellizzari ◽  
Selva Beatriz Cigorraga ◽  
Silvina Beatriz Meroni
Keyword(s):  
Protein Kinase ◽  
Glucose Uptake ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Time Dependent ◽  
Mrna Levels ◽  
Amp Activated Protein Kinase

AbstractThe aim of the present study was to investigate whether the AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in Sertoli cells and whether its activation by 5-aminoimidazole-4-carboxamide-1-b-d-ribonucleoside (AICAR) results in the regulation of cell metabolism to ensure lactate supply for germ cell development. Sertoli cell cultures from 20-day-old rats were used. Western blot analysis for the α-subunit of AMPK showed that high levels of AMPK are present in Sertoli cells. Treatment of the cultures with AICAR resulted in a dose- and time-dependent increase of P-AMPK levels indicating activation of the enzyme. A possible effect of AICAR on Sertoli cell lactate production was then analyzed. A dose- and time-dependent increment in lactate secretion was observed. The participation of AMPK activation in different biochemical processes that may be implicated in the regulation of lactate production was also analyzed. AICAR stimulated glucose uptake in a dose- and time-dependent manner. Additionally, AICAR increased the glucose transporter 1 (GLUT1) and decreased the glucose transporter 3 (GLUT3) mRNA levels. As for the role of AMPK in the regulation of the monocarboxylate transporters 1 and 4 (MCT1 and MCT4), it has been observed that AICAR treatment decreased MCT1 and increased MCT4 mRNA levels. In summary, the results presented herein show that AMPK is present in Sertoli cells and that its activation by AICAR increases lactate production as a result, at least in part, of a) an increase in glucose uptake, b) an increase in GLUT1 expression, and c) a decrease in MCT1 and an increase in MCT4 levels. Altogether, these results suggest an important role of AMPK in modulating the nutritional function of Sertoli cells.

scholarly journals The Role of Phosphoinositide 3-Kinase C2α in Insulin Signaling

2007 ◽  
Vol 282 (38) ◽  
pp. 28226-28236 ◽  
Author(s):  
Marco Falasca ◽  
William E. Hughes ◽  
Veronica Dominguez ◽  
Gianluca Sala ◽  
Florentia Fostira ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Class Ii ◽  
Metabolic Labeling ◽  
Insulin Dependent ◽  
Phosphoinositide 3 Kinase ◽  
Glucose Transporter Glut4

The members of the class II phosphoinositide 3-kinase (PI3K) family can be activated by several stimuli, indicating that these enzymes can regulate many intracellular processes. Nevertheless, to date, there has been no definitive identification of their in vivo product, their mechanism(s) of activation, or their precise intracellular roles. By metabolic labeling, we here identify phosphatidylinositol 3-phosphate as the sole in vivo product of the insulin-dependent activation of PI3K-C2α, confirming the emerging role of such a phosphoinositide in signaling. We demonstrate that activation of PI3K-C2α involves its recruitment to the plasma membrane and that activation is mediated by the GTPase TC10. This is the first report showing a membrane targeting-mediated mechanism of activation for PI3K-C2α and that a small GTP-binding protein can activate a class II PI3K isoform. We also demonstrate that PI3K-C2α contributes to maximal insulin-induced translocation of the glucose transporter GLUT4 to the plasma membrane and subsequent glucose uptake, definitely assessing the role of this enzyme in insulin signaling.

scholarly journals Role of Muscle-Specific Histone Methyltransferase (Smyd1) in Exercise-Induced Cardioprotection against Pathological Remodeling after Myocardial Infarction

2020 ◽  
Vol 21 (19) ◽  
pp. 7010
Author(s):  
Qiaoqin Liang ◽  
Mengxin Cai ◽  
Jiaqi Zhang ◽  
Wei Song ◽  
Wanyu Zhu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Protein Kinase ◽  
Exercise Training ◽  
Cardiac Function ◽  
Histone Methyltransferase ◽  
Ros Generation ◽  
Exercise Induced ◽  
Amp Activated Protein Kinase ◽  
Sarcomere Assembly

Pathological remodeling is the main detrimental complication after myocardial infarction (MI). Overproduction of reactive oxygen species (ROS) in infarcted myocardium may contribute to this process. Adequate exercise training after MI may reduce oxidative stress-induced cardiac tissue damage and remodeling. SET and MYND domain containing 1 (Smyd1) is a muscle-specific histone methyltransferase which is upregulated by resistance training, may strengthen sarcomere assembly and myofiber folding, and may promote skeletal muscles growth and hypertrophy. However, it remains elusive if Smyd1 has similar functions in post-MI cardiac muscle and participates in exercise-induced cardioprotection. Accordingly, we investigated the effects of interval treadmill exercise on cardiac function, ROS generation, Smyd1 expression, and sarcomere assembly of F-actin in normal and infarcted hearts. Adult male rats were randomly divided into five groups (n = 10/group): control (C), exercise alone (EX), sham-operated (S), MI induced by permanent ligation of left anterior descending coronary artery (MI), and MI with interval exercise training (MI + EX). Exercise training significantly improved post-MI cardiac function and sarcomere assembly of F-actin. The cardioprotective effects were associated with increased Smyd1, Trx1, cTnI, and α-actinin expression as well as upregulated ratio of phosphorylated AMP-activated protein kinase (AMPK)/AMPK, whereas Hsp90, MuRF1, brain natriuretic peptide (BNP) expression, ROS generation, and myocardial fibrosis were attenuated. The improved post-MI cardiac function was associated with increased Smyd1 expression. In cultured H9C2 cardiomyoblasts, in vitro treatment with H2O2 (50 µmol/L) or AMP-activated protein kinase (AMPK) agonist (AICAR, 1 mmol/L) or their combination for 4 h simulated the effects of exercise on levels of ROS and Smyd1. In conclusion, we demonstrated a novel role of Smyd1 in association with post-MI exercise-induced cardioprotection. The moderate level of ROS-induced upregulation of Smyd1 may be an important target for modulating post-MI cardiac function and remodeling.

Physiological role of AMP-activated protein kinase (AMPK): insights from knockout mouse models

2003 ◽  
Vol 31 (1) ◽  
pp. 216-219 ◽  
Author(s):  
B. Viollet ◽  
F. Andreelli ◽  
S.B. Jørgensen ◽  
C. Perrin ◽  
D. Flamez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Protein Kinase ◽  
Mouse Models ◽  
Knockout Mouse ◽  
Glycogen Synthesis ◽  
Physiological Role ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To understand better the physiological role of the catalytic AMPK subunit isoforms, we generated two knockout mouse models with the α1 (AMPKα1−/−) and α2 (AMPKα2−/−) catalytic subunit genes deleted. No defect in glucose homoeostasis was observed in AMPKα1−/− mice. On the other hand, AMPKα2−/− mice presented high plasma glucose levels and low plasma insulin concentrations in the fed period and during the glucose tolerance test. Nevertheless, in isolated AMPKα2−/− pancreatic islets, glucose-stimulated insulin secretion was not affected. Surprisingly, AMPKα2−/− mice were insulin-resistant and had reduced muscle glycogen synthesis as assessed in vivo by the hyperinsulinaemic euglycaemic clamp procedure. Reduction of insulin sensitivity and glycogen synthesis were not dependent on the lack of AMPK in skeletal muscle, since mice expressing a dominant inhibitory mutant of AMPK in skeletal muscle were not affected and since insulin-stimulated glucose transport in incubated muscles in vitro was normal in AMPKα2−/− muscles. Furthermore, AMPKα2−/− mice have a higher sympathetic tone, as shown by increased catecholamine urinary excretion. Increased adrenergic tone could explain both decreased insulin secretion and insulin resistance observed in vivo in AMPKα2−/− mice. We suggest that the α2 catalytic subunit of AMPK plays a major role as a fuel sensor by modulating the activity of the autonomous nervous system in vivo.

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