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M Kaur, A L Wooldridge, M J Wilkes, W S Pitchford, P I Hynd, G K McConell, K L Gatford
Intrauterine growth restriction (IUGR) has adverse effects on metabolic health and early life, whereas physical activity is protective against later development of metabolic disease. Relationships between birth weight and physical activity in humans, and effects of IUGR on voluntary activity in rodents, are mixed and few studies have measured physical activity in a free-ranging environment. We hypothesized that induced restriction of placental growth and function (PR) in sheep would decrease spontaneous ambulatory activity (SAA) in free-ranging adolescent and young adult progeny from multi-fetal pregnancies...
June 23, 2016: Journal of Developmental Origins of Health and Disease
Itamar Levinger, Tara C Brennan-Speranza, Nigel K Stepto, George Jerums, Lewan Parker, Glenn K McConell, Mitchell Anderson, Andrew Garnham, David L Hare, Peter R Ebeling, Ego Seeman
BACKGROUND: Undercarboxylated osteocalcin (ucOC) increases insulin sensitivity in mice. In humans, data are supportive, but the studies are mostly cross-sectional. Exercise increases whole-body insulin sensitivity, in part via ucOC, while acute glucocorticoid treatment suppresses ucOC in humans and mice. OBJECTIVES: A single dose of prednisolone reduces the rise in ucOC produced by exercise, which partly accounts for the failed increase in insulin sensitivity following exercise...
2016: JMIR Research Protocols
Andrew C Betik, Jay Aguila, Glenn K McConell, Andrew J McAinch, Michael L Mathai
BACKGROUND AND AIMS: Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. METHODS: Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks...
2016: PloS One
Yet Hoi Hong, Christine Yang, Andrew C Betik, Robert S Lee-Young, Glenn K McConell
Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ(+/+) and nNOSμ(-/-) mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17...
May 15, 2016: American Journal of Physiology. Endocrinology and Metabolism
Shaun A Mason, Dale Morrison, Glenn K McConell, Glenn D Wadley
Recent research highlights the importance of redox signalling pathway activation by contraction-induced reactive oxygen species (ROS) and nitric oxide (NO) in normal exercise-related cellular and molecular adaptations in skeletal muscle. In this review, we discuss some potentially important redox signalling pathways in skeletal muscle that are involved in acute and chronic responses to contraction and exercise. Specifically, we discuss redox signalling implicated in skeletal muscle contraction force, mitochondrial biogenesis and antioxidant enzyme induction, glucose uptake and muscle hypertrophy...
September 2016: Free Radical Biology & Medicine
Glenn D Wadley, Rhianna C Laker, Glenn K McConell, Mary E Wlodek
Being born small for gestational age increases the risk of developing adult cardiovascular and metabolic diseases. This study aimed to examine if early-life exercise could increase heart mass in the adult hearts from growth restricted rats. Bilateral uterine vessel ligation to induce uteroplacental insufficiency and fetal growth restriction in the offspring (Restricted) or sham surgery (Control) was performed on day 18 of gestation in WKY rats. A separate group of sham litters had litter size reduced to five pups at birth (Reduced litter), which restricted postnatal growth...
February 2016: Physiological Reports
Itamar Levinger, Ego Seeman, George Jerums, Glenn K McConell, Mark S Rybchyn, Samantha Cassar, Elizabeth Byrnes, Steve Selig, Rebecca S Mason, Peter R Ebeling, Tara C Brennan-Speranza
Aging is associated with a reduction in osteoblast life span and the volume of bone formed by each basic multicellular unit. Each time bone is resorbed, less is deposited producing microstructural deterioration. Aging is also associated with insulin resistance and hyperglycemia, either of which may cause, or be the result of, a decline in undercarboxylated osteocalcin (ucOC), a protein produced by osteoblasts that increases insulin sensitivity. We examined whether glucose-loading reduces bone remodeling and ucOC in vivo and osteoblast function in vitro, and so compromises bone formation...
February 2016: Physiological Reports
Scott Betteridge, Raúl Bescós, Miquel Martorell, Antoni Pons, Andrew P Garnham, Christos C Stathis, Glenn K McConell
Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design...
February 15, 2016: Journal of Applied Physiology
Itamar Levinger, Tara C Brennan-Speranza, George Jerums, Nigel K Stepto, Fabio R Serpiello, Glenn K McConell, Mitchell Anderson, David L Hare, Elizabeth Byrnes, Peter R Ebeling, Ego Seeman
Bone remodelling markers (BRMs) are suppressed following a glucose load and during glucose infusion. As exercise increases indices of bone health and improves glucose handling, we hypothesised that, at rest, hyperinsulinaemic-euglycaemic clamp will suppress BRMs in obese men and that exercise prior to the clamp will prevent this suppression. Eleven obese nondiabetic men (age 58.1±2.2 years, body mass index=33.1±1.4 kg m(-2) mean±s.e.m.) had a hyperinsulinaemic-euglycaemic clamp (HEC) at rest (Control) and 60 min post exercise (four bouts × 4 min cycling at 95% of hazard ratiopeak)...
2015: BoneKEy Reports
I Levinger, X Lin, X Zhang, T C Brennan-Speranza, B Volpato, A Hayes, G Jerums, E Seeman, G McConell
UNLABELLED: We tested whether GPRC6A, the putative receptor of undercarboxylated osteocalcin (ucOC), is present in mouse muscle and whether ucOC increases insulin sensitivity following ex vivo muscle contraction. GPPRC6A is expressed in mouse muscle and in the mouse myotubes from a cell line. ucOC potentiated the effect of ex vivo contraction on insulin sensitivity. INTRODUCTION: Acute exercise increases skeletal muscle insulin sensitivity. In humans, exercise increases circulating ucOC, a hormone that increases insulin sensitivity in rodents...
February 2016: Osteoporosis International
Craig A Goodman, Derk Pol, Evelyn Zacharewicz, Robert S Lee-Young, Rod J Snow, Aaron P Russell, Glenn K McConell
One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles...
2015: PloS One
Acuña D Aravena, R Pruzzo, N Barrena, H Amaral, P Torres, Y McConell, S Ramírez
No abstract text is available yet for this article.
May 2015: International Journal of Gynecological Cancer
Yet Hoi Hong, Andrew C Betik, Dino Premilovac, Renee M Dwyer, Michelle A Keske, Stephen Rattigan, Glenn K McConell
Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0...
May 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yet Hoi Hong, Tony Frugier, Xinmei Zhang, Robyn M Murphy, Gordon S Lynch, Andrew C Betik, Stephen Rattigan, Glenn K McConell
Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction...
May 1, 2015: Journal of Applied Physiology
Glenn K McConell, Gunveen Kaur, Filippe Falcão-Tebas, Yet H Hong, Kathryn L Gatford
In healthy humans and rodents, chronic and acute exercise improves subsequent insulin sensitivity of skeletal muscle. A large animal species with similar metabolic responses to exercise would permit longitudinal studies, including repeated biopsies of muscle and other tissues not possible in rodents, and enable study of interactions with insulin-resistant physiological states not feasible in humans. Therefore, we examined whether acute exercise increases insulin sensitivity in adult sheep. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp (HEC) in mature female sheep (n = 7)...
March 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Yet Hoi Hong, Andrew C Betik, Glenn K McConell
Nitric oxide is produced within skeletal muscle fibres and has various functions in skeletal muscle. There is evidence that NO may be essential for normal increases in skeletal muscle glucose uptake during contraction/exercise. Although there have been some discrepant results, it has been consistently demonstrated that inhibition of NO synthase (NOS) attenuates the increase in skeletal muscle glucose uptake during contraction in mouse and rat muscle ex vivo, during in situ contraction in rats and during exercise in humans...
December 1, 2014: Experimental Physiology
G D Wadley, M E Wlodek, G Ng, C Goodman, C Stathis, G K McConell
To investigate the mechanisms for the previously reported development of adult cardiac hypertrophy in male rats following growth restriction, the levels of oxidative stress and activation of signaling kinases were measured in the left ventricle (LV) of adult rat offspring. In experiment one, bilateral uterine vessel ligation to induce uteroplacental insufficiency and growth restriction in the offspring (Restricted) or sham surgery was performed during pregnancy. Litters from sham mothers had litter size either reduced (Reduced Litter), which also restricted postnatal growth, or were left unaltered (Control)...
December 2010: Journal of Developmental Origins of Health and Disease
R C Laker, G D Wadley, G K McConell, M E Wlodek
Foetal growth restriction impairs skeletal muscle development and adult muscle mitochondrial biogenesis. We hypothesized that key genes involved in muscle development and mitochondrial biogenesis would be altered following uteroplacental insufficiency in rat pups, and improving postnatal nutrition by cross-fostering would ameliorate these deficits. Bilateral uterine vessel ligation (Restricted) or sham (Control) surgery was performed on day 18 of gestation. Males and females were investigated at day 20 of gestation (E20), 1 (PN1), 7 (PN7) and 35 (PN35) days postnatally...
February 2012: Journal of Developmental Origins of Health and Disease
Itamar Levinger, George Jerums, Nigel K Stepto, Lewan Parker, Fabio R Serpiello, Glenn K McConell, Mitchell Anderson, David L Hare, Elizabeth Byrnes, Peter R Ebeling, Ego Seeman
Acute exercise improves insulin sensitivity for hours after the exercise is ceased. The skeleton contributes to glucose metabolism and insulin sensitivity via osteocalcin (OC) in its undercarboxylated (ucOC) form in mice. We tested the hypothesis that insulin sensitivity over the hours after exercise is associated with circulating levels of ucOC. Eleven middle-aged (58.1 ± 2.2 years mean ± SEM), obese (body mass index [BMI] = 33.1 ± 1.4 kg/m(2) ) nondiabetic men completed a euglycemic-hyperinsulinemic clamp at rest (rest-control) and at 60 minutes after exercise (4 × 4 minutes of cycling at 95% of HRpeak )...
December 2014: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Steven W Yau, Belinda A Henry, Vincenzo C Russo, Glenn K McConell, Iain J Clarke, George A Werther, Matthew A Sabin
Leptin is produced from white adipose tissue and acts primarily to regulate energy balance. Obesity is associated with leptin resistance and increased circulating levels of leptin. Leptin has recently been shown to influence levels of IGF binding protein-2 (IGFBP-2), a protein that is reduced in obesity and type 2 diabetes. Overexpression of IGFBP-2 protects against obesity and type 2 diabetes. As such, IGFBP-2 signaling may represent a novel pathway by which leptin regulates insulin sensitivity. We sought to investigate how leptin regulates skeletal muscle IGFBP-2 levels and to assess the impact of this on insulin signaling and glucose uptake...
June 2014: Endocrinology
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