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Intracellular pH, intrauterine growth and the insulin resistance syndrome

J H Pinkney1, P Vernon, E Carstensen

  • 1Department of Medicine, Clinical Sciences Centre, University Hospital, Aintree, Liverpool, UK.

Clinical Physiology (Oxford, England)
|November 28, 2001
PubMed

Insights

Sodium transport defects are linked to heart disease risk. This study found red blood cell sodium-lithium countertransport (SLC) relates to insulin resistance, while low intracellular pH is linked to low birth weight and adult insulin resistance.

Area of Science:

  • Cardiovascular Science
  • Metabolic Syndrome Research
  • Developmental Origins of Health and Disease (DOHaD)

Background:

  • Defects in sodium-hydrogen exchange (NHE) and sodium-lithium countertransport (SLC) are associated with increased coronary heart disease (CHD) risk.
  • Sodium transport mechanisms are implicated in cellular regulation, potentially explaining links to CHD.
  • Impaired early-life growth is also linked to adult CHD, with 'programmed' cellular alterations proposed as a mechanism.

Purpose of the Study:

  • To investigate if birth anthropometry predicts adult sodium-hydrogen exchange (NHE) or sodium-lithium countertransport (SLC).
  • To examine the association between NHE and SLC in adults with insulin resistance syndrome (IRS) variables.
  • To explore potential 'programmed' cellular phenotypes linking early development to adult cardiovascular and metabolic health.

Main Methods:

  • Red blood cell SLC activity was measured in 26 adults.
  • Sodium-hydrogen exchange (NHE) kinetics (Vmax, Km, Hill coefficient) were measured in dermal fibroblasts from 15 subjects.
  • Subjects were characterized anthropometrically at birth and assessed for IRS variables in adulthood.

Main Results:

  • Red cell SLC activity correlated with LDL cholesterol, triglycerides, and urate, but not with birth anthropometry.
  • NHE Vmax correlated significantly with plasma insulin, but birth weight was not related to NHE kinetics.
  • Intracellular pH (pHi) showed significant correlations with birth weight, insulin sensitivity, fasting glucose, 2-hour insulin, and 2-hour glucose levels.

Conclusions:

  • Red cell SLC is associated with adult insulin resistance syndrome variables but not with birth weight.
  • Low intracellular pH (pHi) is linked to both low birth weight and adult insulin resistance.
  • This suggests intracellular pH may represent a 'programmed' cellular phenotype, though not explained by altered NHE kinetics.

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