Effects of Fetal Insulin Deficiency on Growth in Fetal Lambs

Insulin may be an important regulator of growth in late fetal life. To assess the importance of endogenous insulin release in regulation of normal fetal growth, eight fetal lamb pairs were given either an intravenous injection of streptozocin (STZ), a nitrosourea that selectively damages pancreatic β-cells, or buffer infusion (controls). In six preparations, twins were used, and in two cases, triplets, thus allowing for comparison between treated and control fetuses residing in the same intrauterine environment. Fetal STZ injection was associated with relative fetal hyperglycemia, hypoinsulinemia, and a decrease in the fetal plasma insulin-glucose ratio. Fetal lambs exposed to STZ also developed a mild nonprogressive metabolic acidosis compared with controls. Fetal body weight was depressed by 21% overall, the magnitude of reduction related to length of time in utero after STZ injection. Similar reductions in organ weights (liver, heart, and kidney) were also observed in STZ-administered fetuses compared with controls. Protein accretion in carcass, liver, and kidney after STZ was also depressed, but no significant changes in fetal lipid accretion were observed. Skeletal growth, as measured by tail and tibial lengths, was also depressed after STZ but to a lesser extent than body weight or protein accretion. Thus, in a stable maternal environment, isolated fetal insulin deficiency is associated with significant retardation of somatic and skeletal growth and protein deposition.