**9. Biological functions of IGF-1**

**7. Foetal pancreas development**

76 Umbilical Cord Blood Banking for Clinical Application and Regenerative Medicine

maturation and thus to insulin production.

**8. Growth hormones**

The pancreas is an endocrine and exocrine gland, which plays a major role in our economy. It contributes to the macronutrient digestion by producing enzymes while its endocrine function is critical to glucose homeostasis [1]. In humans, it appears first in gestation at 5–6 weeks, and at 11 weeks the islets can be observed. Insulin production is functional at week 20 [3, 40], and at this time, four cell types can be observed: α-cells producing glucagon, β-cells producing insulin, δ-cells producing somatostatin and PP-cells producing pancreatic polypeptide. As it occurs in adult life, at birth the most abundant cells are the β-cells and the least the PP-cells. The pancreas is an active organ at the end of the first trimester and plays a key role since the fourth month of pregnancy. IGF-1 is fundamental to pancreatic cell specialization, growth, islet

There is a pancreatic plasticity that allows pancreas response to high insulin-demand situations. β-Cell adaptation to different situations (nutrient lack or excess) depends on the equilibrium between cell division, growth and apoptosis death [7]. The foetal β-cell area increases during pregnancy without changing the cell size. However, there is an increase in

IGF-1 is a low-molecular weight peptide hormone, expressed by all the adult and foetal tissues since early life stages. Similar to proinsulin, IGF-1 consists of one single polypeptide chain containing three disulphide bridges inside. Both IGF-1 and proinsulin have identical hydrophobic areas [42]. IGF-1 and its binding proteins (IGFBPs) are powerful stimulators of cellular division and have a very important role in the regulation of foetal growth [18]. After birth, the liver is the main source of IGF-1 and its IGFBPs. Nutritional factors such as protein intake, energy and micronutrients such as zinc regulate IGF-1 synthesis. Hormones such as GH, sexual steroids, thyroid hormones and insulin regulate the expression of IGF-1 and IGFBPs [43, 44].

acumulación de nutrientes

Stimulate fetal growth

the number of small islets, but not of the number of β-cells in each islet [41].

**Hormone Placental GH Human placental lactogen Mother circulation** Liver IGF-1 production Anti-insulinaemic effect

GH, Growth hormone; IGF-1, insulin-like growth factor-1.

**Foetal circulation** Without relevant effects Stimulate liver IGF-1 and glycogenesis

**Table 2.** Effects of placental GH and placental lactogen in both maternal and foetal circulations.

During gestation, pituitary GH production is scarce, while IGF-1 concentration increases, reaching the highest level at the end of pregnancy. This increment is associated with a high

IGF-1 stimulates cartilage growth, DNA, RNA and protein synthesis, and anabolic processes. IGF-1 is a key mediator of hippocampal neurogenesis. GH is expressed in the hippocampus where a high stress regulates it [48]. During pregnancy, IGF-1 stimulates cell division, maternal tissues' growth and anabolic processes resulting in increasing the adipose tissue, liver glycogen reservoir and mammary gland development. IGF-1 has effects that are similar to those of insulin on muscle and placenta, stimulating amino acid and glucose transport and inhibiting lipolysis in the adipose tissue. IGF-1 has also a main role in growth, as the correlation between its concentration and child growth speed shows [49]. In fact, it is the growth factor that best correlates with foetal growth during gestation. The protein-energetic malnutrition and preeclampsia associated with intrauterine growth retardation (IUGR) are two pathologic statuses where IUGR is associated with IGF-1 and IGFBP concentrations. Hypoglycaemia promotes adrenaline release, which stimulates hypothalamus GH release and inhibits insulin production by β-pancreatic cells (**Figure 3**). As indicated, placental GH induces liver IGF-1 production, palliating, at least in part, the negative effects of hypoglycaemia.
