Potential role of skeletal muscle glucose metabolism on the regulation of insulin secretion

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

Download Full-text

Regulation of Insulin Secretion and β-Cell Mass by Activating Signal Cointegrator 2

Molecular and Cellular Biology ◽

10.1128/mcb.01412-05 ◽

2006 ◽

Vol 26 (12) ◽

pp. 4553-4563 ◽

Cited By ~ 15

Author(s):

Seon-Yong Yeom ◽

Geun Hyang Kim ◽

Chan Hee Kim ◽

Heun Don Jung ◽

So-Yeon Kim ◽

...

Keyword(s):

Insulin Secretion ◽

Endocrine Cells ◽

Potential Role ◽

Cell Mass ◽

Dominant Negative ◽

Transcriptional Coactivator ◽

Β Cells ◽

Β Cell ◽

Islet Mass

ABSTRACT Activating signal cointegrator 2 (ASC-2) is a transcriptional coactivator of many nuclear receptors (NRs) and other transcription factors and contains two NR-interacting LXXLL motifs (NR boxes). In the pancreas, ASC-2 is expressed only in the endocrine cells of the islets of Langerhans, but not in the exocrine cells. Thus, we examined the potential role of ASC-2 in insulin secretion from pancreatic β-cells. Overexpressed ASC-2 increased glucose-elicited insulin secretion, whereas insulin secretion was decreased in islets from ASC-2+/− mice. DN1 and DN2 are two dominant-negative fragments of ASC-2 that contain NR boxes 1 and 2, respectively, and block the interactions of cognate NRs with the endogenous ASC-2. Primary rat islets ectopically expressing DN1 or DN2 exhibited decreased insulin secretion. Furthermore, relative to the wild type, ASC-2+/− mice showed reduced islet mass and number, which correlated with increased apoptosis and decreased proliferation of ASC-2+/− islets. These results suggest that ASC-2 regulates insulin secretion and β-cell survival and that the regulatory role of ASC-2 in insulin secretion appears to involve, at least in part, its interaction with NRs via its two NR boxes.

Download Full-text

Abstract 112: A Pathological Role of Endothelial p53 in the Regulation of Endothelial Function and Glucose Metabolism

Circulation Research ◽

10.1161/res.113.suppl_1.a112 ◽

2013 ◽

Vol 113 (suppl_1) ◽

Author(s):

Masataka YOKOYAMA ◽

Yoshio KOBAYASHI ◽

Tohru MINAMINO

Keyword(s):

Skeletal Muscle ◽

Endothelial Cell ◽

Glucose Metabolism ◽

Endothelial Function ◽

Mitochondrial Biogenesis ◽

Glucose Transporter ◽

Diabetic Patients ◽

Glucose Transporter 1 ◽

P53 Activation

Cellular senescence is a state of irreversible growth arrest induced by various stresses such as oncogenic stimuli. This response is controlled by negative regulators of the cell cycle like the p53 tumor suppressor protein. Accumulating evidence has suggested a role of p53 activation in various age-associated conditions including atherosclerosis, heart failure and diabetes. Here we show that endothelial p53 activation plays a pathological role in the regulation of endothelial function and glucose metabolism under diabetic conditions. Endothelial expression of p53 was markedly up-regulated in a streptozotocin-induced diabetes model. Endothelial function such as acetylcholine-dependent vasodilatation was markedly impaired in this model. Although hyperglycemia was not altered, impairment of endothelial function was significantly improved in mice with endothelial cell-specific p53 deficiency. In same way, p53 was markedly activated in ischemic vessels, and endothelial p53 deficiency enhanced ischemia-induced angiogenesis. Mechanistically, endothelial p53 up-regulated the expression of PTEN that negatively regulated the Akt-eNOS pathway, and therefore disruption of p53 improved endothelial dysfunction. We also found that endothelial p53 was markedly activated, and the Akt-eNOS pathway was attenuated in a diet-induced obesity model. Disruption of endothelial p53 activation improved dietary inactivation of eNOS that up-regulated the expression of PGC-1α in skeletal muscle, thereby increasing mitochondrial biogenesis and oxygen consumption. Inhibition of endothelial p53 also improved dietary impairment of glucose transport into skeletal muscle by up-regulating endothelial expression of glucose transporter 1. Consequently, mice with endothelial cell-specific p53 deficiency fed a high-calorie diet showed improvement of insulin sensitivity and less fat accumulation compared with control littermates. These results indicate that endothelial p53 negatively regulates endothelium-dependent vasodilatation, ischemia-induced angiogenesis, and mitochondrial biogenesis by inhibiting the Akt-eNOS pathway and suggest that inhibition of endothelial p53 could be a novel therapeutic target in diabetic patients.

Download Full-text

Appendicular lean mass is lower in late compared with early perimenopausal women: potential role of FSH

Journal of Applied Physiology ◽

10.1152/japplphysiol.00315.2019 ◽

2020 ◽

Vol 128 (5) ◽

pp. 1373-1380

Author(s):

Young-Min Park ◽

Catherine M. Jankowski ◽

Cemal Ozemek ◽

Kerry L. Hildreth ◽

Wendy M. Kohrt ◽

...

Keyword(s):

Skeletal Muscle ◽

Lean Mass ◽

Potential Role ◽

Appendicular Lean Mass ◽

Vulnerable Period ◽

Perimenopausal Women

Our data suggest that the late perimenopausal stage may be a vulnerable period for the loss of skeletal muscle, potentially related to elevations in FSH.

Download Full-text

The Potential Role of Insulin-Like Growth Factors in Skeletal Muscle Regeneration

Canadian Journal of Applied Physiology ◽

10.1139/h96-021 ◽

1996 ◽

Vol 21 (4) ◽

pp. 236-250 ◽

Cited By ~ 19

Author(s):

Jamie MacGregor ◽

Wade S. Parkhouse

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Growth Factors ◽

Muscle Regeneration ◽

Potential Role ◽

Tissue Growth ◽

Skeletal Muscle Regeneration ◽

Tissue Type ◽

Insulin Like Growth Factors

The role of the insulin-like growth factors I and II (IGF-I and IGF-II), previously known as the somatomedins, in general growth and development of various tissues has been known for many years. Thought of exclusively as endocrine factors produced by the liver, and under the control of growth hormone, the somatomedins were known as the intermediaries by which growth hormone exerted its cellular effects during tissue growth and maturation. Eventually it was discovered that virtually every tissue type is capable of autocrine production of the IGFs, and their involvement in skeletal muscle tissue repair and regeneration became apparent. Recent advances in technology have allowed the characterisation of many of the different growth factors believed to play a role in muscle regeneration, and experimental manipulations of cells in culture have provided insight into the effects of the various growth factors on the myoblast. This paper explores the potential role of the IGFs in skeletal muscle regeneration. A critical role of IGF-II in terminal differentiation of proliferating muscle precurser cells following injury is proposed. Key words: growth factors, myogenesis, skeletal muscle regeneration

Download Full-text

Abstract 14297: Potential Role of the Tumor Suppressor WWOX in Mediating Skeletal Muscle-Lung Vasculature Crosstalk in PH-HFpEF

Circulation ◽

10.1161/circ.142.suppl_3.14297 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Gunner Halliday ◽

Yang Bai ◽

Marta T Gomes ◽

Dmitry Goncharov ◽

Elena Goncharova ◽

...

Keyword(s):

Skeletal Muscle ◽

Tumor Suppressor ◽

Potential Role ◽

Pulmonary Vascular Remodeling ◽

Expression Levels ◽

Promote Cell Proliferation ◽

Pulmonary Arterial ◽

Arterial Smooth Muscle Cells ◽

Group 2

Introduction: Pulmonary hypertension due to left heart disease (PH-LHD; Group 2), particularly in the context of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide. At present, no specific effective therapy has been identified mainly due to the fact that major pathways involved in the regulation of PH-HFpEF are still not well understood. Results: We have recently reported on a role of skeletal muscle sirtuin-3 (SIRT3) in modulating PH-HFpEF. Using skeletal muscle-specific SIRT3 knockout mice ( Sirt3 skm-/- ), we showed that absence of SIRT3 in skeletal muscle drastically reduced the pulmonary vascular tree accompanied by vascular proliferative remodeling. Interestingly, we found that expression levels of the tumor suppressor WW domain-containing oxidoreductase (WWOX) were decreased in pulmonary arterial smooth muscle cells (PASMCs) obtained from Sirt3 skm-/- mice, while no changes in SIRT3 activation levels were detected. Reduced WWOX expression levels were also found in PASMCs isolated from SU5416/Obese ZSF1 (Ob-Su) rat model of PH-HFpEF, in which the levels of SIRT3 activation were found to be decreased in skeletal muscle, but not in the lungs and PASMCs. No changes of WWOX levels were observed in skeletal muscle of Ob-Su rats or in pulmonary artery endothelial cells (PAECs) treated with plasma obtained from Ob-Su rats. Conclusions: Since reduction of WWOX in PASMCs has been shown to promote cell proliferation, HIF1α stabilization and pulmonary arterial hypertension (PAH; Group 1), our data suggest a potential role of WWOX in mediating skeletal muscle SIRT3 deficiency-associated remote pulmonary vascular remodeling in PH-HFpEF.

Download Full-text

Transgenic overexpression of intraislet ghrelin does not affect insulin secretion or glucose metabolism in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00341.2011 ◽

2012 ◽

Vol 302 (4) ◽

pp. E403-E408 ◽

Cited By ~ 8

Author(s):

Mika Bando ◽

Hiroshi Iwakura ◽

Hiroyuki Ariyasu ◽

Hiroshi Hosoda ◽

Go Yamada ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Metabolism ◽

Medium Chain Triglyceride ◽

Physiological Role ◽

Standard Diet ◽

Entry Site ◽

Insulin Secretion In Vivo

Whereas ghrelin is produced primarily in the stomach, a small amount of it is produced in pancreatic islets. Although exogenous administration of ghrelin suppresses insulin secretion in vitro or in vivo, the role of intraislet ghrelin in the regulation of insulin secretion in vivo remains unclear. To understand the physiological role of intraislet ghrelin in insulin secretion and glucose metabolism, we developed a transgenic (Tg) mouse model, rat insulin II promoter ghrelin-internal ribosomal entry site-ghrelin O-acyl transferase (RIP-GG) Tg mice, in which mouse ghrelin cDNA and ghrelin O-acyltransferase are overexpressed under the control of the rat insulin II promoter. Although pancreatic desacyl ghrelin levels were elevated in RIP-GG Tg mice, pancreatic ghrelin levels were not altered in animals on a standard diet. However, when Tg mice were fed a medium-chain triglyceride-rich diet (MCTD), pancreatic ghrelin levels were elevated to ∼16 times that seen in control animals. It seems likely that the gastric ghrelin cells possess specific machinery to provide the octanoyl acid necessary for ghrelin acylation but that this machinery is absent from pancreatic β-cells. Despite the overexpression of ghrelin, plasma ghrelin levels in the portal veins of RIP-GG Tg mice were unchanged from control levels. Glucose tolerance, insulin secretion, and islet architecture in RIP-GG Tg mice were not significantly different even when the mice were fed a MCTD. These results indicate that intraislet ghrelin does not play a major role in the regulation of insulin secretion in vivo.

Download Full-text

The production of reactive oxygen and nitrogen species by skeletal muscle

Journal of Applied Physiology ◽

10.1152/japplphysiol.01102.2006 ◽

2007 ◽

Vol 102 (4) ◽

pp. 1664-1670 ◽

Cited By ~ 125

Author(s):

Malcolm J. Jackson ◽

Deborah Pye ◽

Jesus Palomero

Keyword(s):

Nitric Oxide ◽

Skeletal Muscle ◽

Potential Role ◽

Reactive Oxygen ◽

Oxygen Species ◽

Nitrogen Species ◽

Redox Biology ◽

Controlled Systems ◽

Potential Source

Skeletal muscle has been recognized as a potential source for generation of reactive oxygen and nitrogen species for more than 20 years. Initial investigations concentrated on the potential role of mitochondria as a major source for generation of superoxide as a “by-product” of normal oxidative metabolism, but recent studies have identified multiple subcellular sites, where superoxide or nitric oxide are generated in regulated and controlled systems in response to cellular stimuli. Full evaluation of the factors regulating these processes and the functions of the reactive oxygen species generated are important in understanding the redox biology of skeletal muscle.

Download Full-text

Skeletal muscle and resistance exercise training; the role of protein synthesis in recovery and remodeling

Journal of Applied Physiology ◽

10.1152/japplphysiol.00613.2016 ◽

2017 ◽

Vol 122 (3) ◽

pp. 541-548 ◽

Cited By ~ 31

Author(s):

Chris McGlory ◽

Michaela C. Devries ◽

Stuart M. Phillips

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Protein Turnover ◽

Potential Role ◽

Muscle Protein ◽

Short Review ◽

Translational Efficiency ◽

Exercise Science ◽

Resistance Exercise Training

Exercise results in the rapid remodeling of skeletal muscle. This process is underpinned by acute and chronic changes in both gene and protein synthesis. In this short review we provide a brief summary of our current understanding regarding how exercise influences these processes as well as the subsequent impact on muscle protein turnover and resultant shift in muscle phenotype. We explore concepts of ribosomal biogenesis and the potential role of increased translational capacity vs. translational efficiency in contributing to muscular hypertrophy. We also examine whether high-intensity sprinting-type exercise promotes changes in protein turnover that lead to hypertrophy or merely a change in mitochondrial content. Finally, we propose novel areas for future study that will fill existing knowledge gaps in the fields of translational research and exercise science.

Download Full-text