Article
Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight.
Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark.
Journal of Clinical Endocrinology & Metabolism (impact factor:
6.5).
05/2007;
92(4):1530-4.
DOI:10.1210/jc.2006-2360
pp.1530-4
Source: PubMed
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Citations (0)
- Cited In (3)
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Article: Altered PI3-kinase/Akt signalling in skeletal muscle of young men with low birth weight.
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ABSTRACT: Low birth weight (LBW) is associated with increased future risk of insulin resistance and type 2 diabetes mellitus. The underlying molecular mechanisms remain poorly understood. We have previously shown that young LBW men have reduced skeletal muscle expression of PI3K p85alpha regulatory subunit and p110beta catalytic subunit, PKCzeta and GLUT4 in the fasting state. The aim of this study was to determine whether insulin activation of the PI3K/Akt and MAPK signalling pathways is altered in skeletal muscle of young adult men with LBW. Vastus lateralis muscle biopsies were obtained from 20 healthy 19-yr old men with BW< or = 10th percentile for gestational age (LBW) and 20 normal birth weight controls (NBW), matched for physical fitness and whole-body glucose disposal, prior to (fasting state) and following a 4-hr hyperinsulinemic euglycemic clamp (insulin stimulated state). Expression and phosphorylation of selected proteins was determined by Western blotting. Insulin stimulated expression of aPKCzeta (p<0.001) and Akt1 (p<0.001) was decreased in muscle of LBW men when compared to insulin stimulated controls. LBW was associated with increased insulin stimulated levels of IRS1 (p<0.05), PI3K p85alpha (p<0.001) and p110beta (p<0.05) subunits, while there was no significant change in these proteins in insulin stimulated control muscle. In addition LBW had reduced insulin stimulated phospho-Akt (Ser 473) (p<0.01), indicative of reduced Akt signalling. Insulin stimulated expression/phosphorylation of all the MAPK proteins studied [p38 MAPK, phospho-p38 MAPK (Thr180/Tyr182), phospho-ERK (Thr 202/Tyr204), JNK1, JNK2 and phospho-JNK (Thr 183/Tyr185)] was not different between groups. We conclude that altered insulin activation of the PI3K/Akt but not the MAPK pathway precedes and may contribute to development of whole-body insulin resistance and type 2 diabetes in men with LBW.PLoS ONE 01/2008; 3(11):e3738. · 4.09 Impact Factor -
Article: Birth weight in relation to leisure time physical activity in adolescence and adulthood: meta-analysis of results from 13 nordic cohorts.
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ABSTRACT: Prenatal life exposures, potentially manifested as altered birth size, may influence the later risk of major chronic diseases through direct biologic effects on disease processes, but also by modifying adult behaviors such as physical activity that may influence later disease risk. We investigated the association between birth weight and leisure time physical activity (LTPA) in 43,482 adolescents and adults from 13 Nordic cohorts. Random effects meta-analyses were performed on categorical estimates from cohort-, age-, sex- and birth weight specific analyses. Birth weight showed a reverse U-shaped association with later LTPA; within the range of normal weight the association was negligible but weights below and above this range were associated with a lower probability of undertaking LTPA. Compared with the reference category (3.26-3.75 kg), the birth weight categories of 1.26-1.75, 1.76-2.25, 2.26-2.75, and 4.76-5.25 kg, had odds ratios of 0.67 (95% confidence interval: 0.47, 0.94), 0.72 (0.59, 0.88), 0.89 (0.79, 0.99), and 0.65 (0.50, 0.86), respectively. The shape and strength of the birth weight-LTPA association was virtually independent of sex, age, gestational age, educational level, concurrent body mass index, and smoking. The association between birth weight and undertaking LTPA is very weak within the normal birth weight range, but both low and high birth weights are associated with a lower probability of undertaking LTPA, which hence may be a mediator between prenatal influences and later disease risk.PLoS ONE 01/2009; 4(12):e8192. · 4.09 Impact Factor -
Article: Hertfordshire sarcopenia study: design and methods.
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ABSTRACT: Sarcopenia is defined as the loss of muscle mass and strength with age. Although a number of adult influences are recognised, there remains considerable unexplained variation in muscle mass and strength between older individuals. This has focused attention on influences operating earlier in life. Our objective for this study was to identify life course influences on muscle mass and strength in an established birth cohort and develop methodology for collection of muscle tissue suitable to investigate underlying cellular and molecular mechanisms. One hundred and five men from the Hertfordshire Cohort Study (HCS), born between 1931 and 1939 who have historical records of birth weight and weight at one year took part in the Hertfordshire Sarcopenia Study (HSS). Each participant consented for detailed characterisation of muscle mass, muscle function and aerobic capacity. In addition, a muscle biopsy of the vastus lateralis using a Weil-Blakesley conchotome was performed. Data on muscle mass, function and aerobic capacity was collected on all 105 participants. Muscle biopsy was successfully carried out in 102 participants with high rates of acceptability. No adverse incidents occurred during the study. The novel approach of combining epidemiological and basic science characterisation of muscle in a well established birth cohort will allow the investigation of cellular and molecular mechanisms underlying life course influences on sarcopenia.BMC Geriatrics 01/2010; 10:43. · 2.34 Impact Factor
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Keywords
adverse fetal environment
adverse fetal milieu
birth weights
body fat
classify muscle fibers
fiber composition
future risk
insulin resistance
insulin-stimulated glycolysis
Low birth weight
muscle insulin resistance
Myofibrillar ATPase staining
percutaneous biopsy
Skeletal muscle mass
type 2 diabetes
type IIa fibers
type IIb
type IIx fibers
Vastus lateralis muscle
whole-body glucose disposal