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Intracellular pH, intrauterine growth and the insulin resistance syndrome

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Defects of both sodium–hydrogen exchange (NHE) and sodium–lithium countertransport (SLC) have been described in subjects at increased risk of coronary heart disease (CHD). Sodium transport is linked to the regulation of cell volume, intracellular pH and cell growth, which may explain aspects of this association. However, impaired growth in early life is also linked to adult CHD, and ‘programmed’ alterations of cell behaviour are postulated to be responsible for this. In this study, therefore, we examined whether NHE or SLC in adults are predicted by anthropometric measures at birth, as well as being associated with insulin resistance syndrome (IRS) variables in adulthood. Red cell SLC was measured in 26 adults, and NHE in dermal fibroblasts from another 15 subjects characterized anthropometrically at birth. SLC activity correlated with LDL cholesterol, triglycerides and urate (r=0·42 – 0·49; 0·05 > P>0·01), but not birth anthropometry. NHE Vmax correlated with plasma insulin (r=0·80; P<0·001), but birth weight was unrelated to Vmax, Km or Hill coefficient for H+i. However, pHi correlated with birth weight (r=0·74; P=0·002), insulin sensitivity (r=0·52; P<0·05), fasting glucose (r=–0·52; P<0·05) 2 h insulin (r=0·51; P<0·05) 2 h glucose (r=–0·54; P<0·05). In conclusion, red cell SLC is related to IRS variables, but not with birth weight measures. In contrast, low intracellular pHi is related to both low birth weight and adult insulin resistance, suggesting it might be a ‘programmed’ cell phenotype, although this is not apparently explained by altered NHE kinetics.
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Keywords: birthweight; cardiovascular risk factors; insulin resistance; intracellular pH; sodium–hydrogen exchange; sodium–lithium countertransport

Document Type: Research Article

Affiliations: 1: University College London School of Medicine, Whittington Hospital, London, UK 2: University of Southampton, MRC Environmental Epidemiology Department, Southampton General Hospital, Southampton, UK

Publication date: November 1, 2001

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