Imprinting of female offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats

The Journal of Clinical Investigation
C NilssonAgneta Holmäng

Abstract

In women, a relative hyperandrogenicity is statistically associated with insulin resistance and centralization of body fat, which are predictors for the development of non-insulin-dependent diabetes mellitus. The aim of this study was to evaluate the effect of androgenization of newborn female rats on insulin sensitivity at adult age. To mimic the neonatal androgen peak normally observed in male rats, female pups were administered one high dose of testosterone (T) subcutaneously within 3 h after birth. They were then given back to their mothers and followed to adult age. At the end of the week 9, tail samples were taken, showing no differences in fasting plasma concentrations of glucose, lactate, insulin, or free fatty acids between T-treated rats and controls. Plasma concentrations of T and progesterone were significantly lower in the T-treated rats, whereas no differences were found in the levels of corticosterone, estradiol, insulin-like growth factor I, or ACTH. After 10 wk, insulin sensitivity was studied with hyperglycemic and euglycemic hyperinsulinemic (5 mU insulin/kg/min) clamp techniques. The T-treated rats showed insulin resistance with both techniques, which was overcome with time and increasing insulin concentrati...Continue Reading

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