Transgenerational endocrine pancreatic adaptation in mice from maternal protein restriction in utero

Abstract

Exposure of pregnant mice to a low-protein diet (LP) impairs endocrine pancreas development in their offspring. There is evidence that this phenomenon may persist in subsequent generations. Here, we evaluated the effect of LP on glucose metabolism and pancreatic morphometry in the F3 offspring of mice at birth and weaning. LP pups in the first generation were smaller at birth, but catch-up growth; F2-LP offspring had higher body mass at birth, but there was no difference in the F3 generation. The pancreatic mass decreased in F1-LP through F3-LP at birth but increased in F2-LP at weaning. The islet volume density and diameter were smaller in all restricted groups at day 1 and 21, and F1-LP had the lowest islet number; at birth, beta cell mass was smaller in F1-LP through F3-LP and remained low throughout suckling. At day 1 and 21, pups were normoglycemic, but were hypoinsulinemic at weaning. Thus, protein restriction in mice during pregnancy produces morphologic changes in pancreatic islets, suggesting that glucose homeostasis is maintained by an increased sensitivity to insulin during the early stages of life in offspring over three consecutive generations.