Fetal Growth and Insulin Resistance in Adult Life: Relationship Between Glycogen Synthase Activity in Adult Skeletal Muscle and Birthweight

Phillips, David I. W.; Borthwick, A C; Stein, C.M.; Taylor, Roy

doi:10.1002/(sici)1096-9136(199604)13:4<325::aid-dia79>3.0.co;2-s

Cited by 21 publications

(5 citation statements)

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“…Furthermore, impaired mitochondrial function and oxidative phosphorylation in skeletal muscle has been shown in rats experiencing growth retardation in utero (28). In humans, the postprandial activity of glycogen synthase in skeletal muscle, which is the rate-limiting step in muscle glycogen synthesis, was not related to intrauterine growth as evidenced by birth weight (29). We found a clear positive association between birth weight and glucose oxidation in elderly singletons, whereas glucose oxidation was similar in elderly singletons and twins.…”

Section: Discussionsupporting

confidence: 87%

The Intrauterine Environment as Reflected by Birth Size and Twin and Zygosity Status Influences Insulin Action and Intracellular Glucose Metabolism in an Age- or Time-Dependent Manner

Poulsen

Vaag

2006

Diabetes

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According to the "fetal origins hypothesis," monozygotic (MZ) twins may be more prone to develop various metabolic abnormalities compared with dizygotic (DZ) twins, and twins all together may be more predisposed to metabolic defects compared with singletons. To determine the impact of twin and zygosity status as well as birth size on in vivo measures of glucose metabolism, we examined 123 young (aged 22-31 years) and 103 elderly (aged 57-66 years) MZ and DZ twins and age-matched singleton control subjects. All participants were born at term with available birth records. Peripheral and hepatic insulin action and intracellular glucose partitioning was determined by a euglycemic-hyperinsulinemic clamp using tritiated glucose combined with indirect calorimetry. In elderly subjects, zygosity status influenced nonoxidative glucose metabolism, while twin status per se was associated with elevated hepatic glucose production during both steady-state periods. Birth weight was associated with nonoxidative glucose metabolism in a nongenetic manner within twins and with a high glucose and low lipid oxidation in singletons. In younger subjects, twin status influenced glucose and lipid oxidation rates. We demonstrate a complex age-or timedependent relationship between independent markers of fetal environment and glucose homeostasis in twins. The documented differential programming effects associated with either low birth weight and twin or zygosity status all represent known defects of glucose homeostasis in type 2 diabetes. Diabetes 55: 1819 -1825, 2006 F etal growth restriction is more likely to occur in twins compared with singletons because of their shared uterine environment. Monozygotic (MZ) twins are often monochorionic and share the same placenta and nutritive source and may consequently have a different and potentially more adverse intrauterine environment compared with dizygotic (DZ) and dichorionic MZ twins having separate placentas (1). According to the "fetal origins hypothesis," MZ twins may therefore be more prone to develop various metabolic abnormalities compared with DZ twins, and twins all together may be more predisposed to metabolic impairments compared with singletons.It has been questioned whether the factors regulating intrauterine growth in twin and singleton pregnancies are similar (2). Likewise, it is unknown whether the putative effect of intrauterine growth restriction on the development of adult diseases differs between twins and singletons (3). A Danish twin study (4) demonstrated similar longevity/death rates in a selected group of MZ and DZ twin pairs both surviving the age of 6 years compared with singletons. Other studies (5-7), however, have shown differences in prevalence of cancer among MZ and DZ twins versus singletons. We recently demonstrated reduced insulin sensitivity in elderly MZ compared with DZ twins (8,9). Conversely, young MZ twins were slightly more insulin sensitive than young DZ twins (9), indicating an age-or time-dependent effect of the fetal environment on glucose homeo...

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Section: Discussionsupporting

confidence: 87%

The Intrauterine Environment as Reflected by Birth Size and Twin and Zygosity Status Influences Insulin Action and Intracellular Glucose Metabolism in an Age- or Time-Dependent Manner

Poulsen

Vaag

2006

Diabetes

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“…Previous studies have failed to demonstrate any influence of birth weight on postprandial GS activity (18) or on basal or insulin-stimulated GS gene expression levels (19) in relatively young human subjects. The significant positive association between birth weight and muscle glycogen content in elderly twins in the present study is consistent with studies reporting reduced muscle and liver glycogen contents in rats exposed to protein restriction during fetal life (20,21).…”

Section: Discussionmentioning

confidence: 48%

“…The significant positive association between birth weight and muscle glycogen content in elderly twins in the present study is consistent with studies reporting reduced muscle and liver glycogen contents in rats exposed to protein restriction during fetal life (20,21). It is likely that the lack of association between birth weight and GS activity and regulation in previous human studies may be explained by a relatively small number of study subjects, differences in age, and perhaps most importantly by the failure to adjust for genetic influence (18,19). The defect in GS activity associated with low birth weight is mediated by increased GSK3␣ activity and GS phosphorylation and may represent an independent mechanism linking fetal environment and insulin resistance or may operate in concert with additional underlying defects of insulin signaling.…”

Section: Discussionmentioning

confidence: 99%

Low Birth Weight and Zygosity Status Is Associated With Defective Muscle Glycogen and Glycogen Synthase Regulation in Elderly Twins

et al. 2007

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OBJECTIVE— An adverse intrauterine environment indicated by both low birth weight and monozygosity is associated with an age- or time-dependent reduction in glucose disposal and nonoxidative glucose metabolism in twins, suggesting impaired regulation of muscle glycogen synthesis. RESEARCH DESIGN AND METHODS— We measured the activities of glycogen synthase (GS), GS kinase (GSK)3α, GS phosphorylation, and glycogen levels in muscle biopsies obtained from 184 young and elderly twins before and after a euglycemic-hyperinsulinemic clamp. RESULTS— Elderly monozygotic twins had significantly lower fractional GS activity amidst higher glycogen and GS protein levels compared with dizygotic twins. In addition, we demonstrated strong nongenetic associations between birth weight and defect muscle glycogen metabolism in elderly—but not in younger—twins. Thus, for every 100 g increase in birth weight within pairs, GS fractional activity, GS protein level, and glycogen content was increased by 4.2, 8.7, and 4.5%, respectively, in elderly twins. Similarly, for every 100 g increase in birth weight, GSK3α activity and GS phosphorylation at the sites 2, 2+2a, and 3a+3b were decreased by 3.1, 9.0, 10.1, and 9.5%, respectively. CONCLUSIONS— The age- or time-dependent nongenetic impact of birth weight on insulin action in twins may partly be explained by reduced insulin activation of muscle GS, mediated through increased GSK3α activity and GS phosphorylation. Reduced GS activity and negative feedback inhibition of glycogen metabolism by glycogen per se may contribute to the insulin resistance in elderly monozygotic compared with dizygotic twins.

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“…The papers which were excluded, together with the reasons for exclusion, are given in Table 6[51–70].…”

Section: Resultsmentioning

confidence: 99%

Is birth weight related to later glucose and insulin metabolism?—a systematic review

et al. 2003

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Fetal Growth and Insulin Resistance in Adult Life: Relationship Between Glycogen Synthase Activity in Adult Skeletal Muscle and Birthweight

Cited by 21 publications

References 0 publications

The Intrauterine Environment as Reflected by Birth Size and Twin and Zygosity Status Influences Insulin Action and Intracellular Glucose Metabolism in an Age- or Time-Dependent Manner

The Intrauterine Environment as Reflected by Birth Size and Twin and Zygosity Status Influences Insulin Action and Intracellular Glucose Metabolism in an Age- or Time-Dependent Manner

Low Birth Weight and Zygosity Status Is Associated With Defective Muscle Glycogen and Glycogen Synthase Regulation in Elderly Twins

Is birth weight related to later glucose and insulin metabolism?—a systematic review

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