Expression of Insulin-Like Growth Factors (IGFs) and Their Binding Proteins (IGF BPs) During Pancreatic Development in Rat, and Modulation of IGF Actions on Rat Islet DNA Synthesis by IGF BPs

Abstract

Growth of pancreatic β-cells is an essential feature of fetal development in order to maintain insulin needs. This is particularly relevant to the growth of the mammalian fetus where there is an ever-increasing demand for insulin both to facilitate the metabolic processes of growth, and to act as a peptide growth factor.¹ An increase in β cell mass may be derived not only from β-cell replication but from the recruitment and maturation of undifferentiated β-cell precursors. In the rat fetus the cellular area staining positively for insulin by immunohistochemistry increases two-fold within two days of the end of gestation. However, only 20% of this increase can be accounted for by the proliferation rate of existing β-cells.² The maturation of precursor cells is supported by the observation that DNA synthesis in cells next to growing islets proceeds at a faster rate than in the islets themselves. Similarly, the newborn rat, made diabetic with streptozotocin, exhibits serious β-cell destruction, but at 14 days after birth demonstrates normo-glycemia with considerable mitotic activity being apparent in the non-endocrine cells and the duct epithelium of the pancreas.³ While metabolic and nutritional control of β cell hyperplasia is well documented,⁴ there is a growing cohort of reports that suggest that an endogenous production of growth factors including insulin-like growth factor (IGF)-I and-II may also contribute to the process.^5-9