The Role of Insulin and Glucagon in Fetal Growth and Metabolism

1984

Clinical Endocrinology

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127

Both insulin and the related peptides, the insulin-like growth factors/somatomedins, may function as anabolic factors in the regulation of fetal body size. Infants born to women suffering from diabetes mellitus may show increased deposition of subcutaneous fat and enhanced lean body mass, findings reproduced in experimental animal fetuses with induced hyperinsulinaemia. Fetal adiposity may be associated with a life-time tendency to obesity and its associated diseases. Insulin-like growth factors I (IGFI) and II are present in the circulation of the newborn infant and animal fetus and correlate positively with birth size. The fetal tissues are biologically responsive to IGFs in vitro and are rich in specific cell membrane receptors, those predominantly recognizing IGFI being structurally and functionally similar to the insulin receptor. Insulin could theoretically influence fetal tissues by an interaction with either the insulin or IGF receptor. IGF release is a property of multiple fetal tissues in vitro, but, in contrast to postnatal life, is not dependent on growth hormone. Fetal IGF production may be influenced by placental lactogen, especially IGFII which rapidly declines in the circulation following parturition in the rat and sheep. A positive association also exists between circulating levels of insulin and IGFs when the former is experimentally manipulated in the animal fetus. Similarly the infant born with transient diabetes mellitus has low cord blood levels of insulin and IGFI. Insulin has a dual role in prenatal life. In the last trimester insulin functions as a glucoregulatory hormone, but from much earlier in gestation creates an anabolic environment in the fetus supplied with optimal nutrients. This latter mechanism of action is unclear and probably heterogeneous, but in overview is permissive rather than obligatory. In contrast the growth-promoting role of the IGFs is direct but their interaction with fetal tissues, and thus the overall emphasis of fetal growth, may be paracrine.

Section: Insulinmentioning

confidence: 99%

Fetal Growth Control: The Role of Insulin and Related Peptides

1984

Clinical Endocrinology

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127

“…Insulin may have a profound effect on fetal metabolism and body weight as seen in the heavy, hyperinsulinaemic infants of untreated diabetic mothers and the low birthweight of infants with diabetes mellitus [1]. Much of the weight discrepancy can be accounted for by excess or reduced adipose tissue, and to a lesser extent by alterations in visceral mass [2].…”

Section: Chemicalsmentioning

confidence: 99%

Increased somatomedin and cartilage metabolic activity in rabbit fetuses injected with insulin in utero

1980

Diabetologia

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The effect of insulin injection in fetal rabbits on plasma somatomedin activity and cartilage metabolism was investigated. One fetus in each of 12 litters was injected with 1 unit of insulin zinc suspension subcutaneously on day 27 of gestation and a control fetus was injected with the same volume of 0.154 mol/l saline. The litter was delivered by caesarean section on day 29 and each fetus identified. Plasma somatomedin activity was determined by fetal rabbit cartilage bioassay. Costal cartilage from individual fetuses was incubated in medium containing [3H]thymidine or [35S]sulphate as indicators of cell replication and matrix synthesis respectively. Individual values for somatomedin activity or cartilage isotope uptake were ranked within a litter. In each case the rank in the litter of the insulin-injected fetus, but not the saline-injected fetus, was significantly higher than the mean rank of the litter. Insulin did not stimulate cartilage metabolism in vitro.

“…These three elements are interdependent and act in unison to provide conditions that optimize fetal cellular development. Elsewhere we have reviewed fetal growth from different angles: a general review of prenatal growth control in man [90], the contrasting effects of insulin and glucagon on fetal metabolism [87], fetal carbohydrate and fat metabolism [89], insulin as a growth factor before and after birth [57], the role of insulin and related peptides in fetal growth [58] and growth factors in embryogenesis [66].…”

Section: Introductionmentioning

confidence: 99%

Interaction between endocrine and paracrine peptides in prenatal growth control

1987

Eur J Pediatr

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The evidence reviewed here shows that the endocrinology of fetal growth is very different from that operating postnatally. Pituitary hormones play little part in stimulating growth of the lean body mass or skeleton although growth hormone (GH) may be involved, in some as yet ill defined way in the ontogeny of the fetal pancreatic islet and insulin secretion. Insulin is important because it stimulates fetal cellular anabolism but acts in a permissive manner: with too little insulin growth is inhibited, with too much growth proceeds at a genetically predetermined rate. Placental lactogen (PL), or other peptides within the GH/PL family, may act as a true growth-promoting hormone in the fetus; it stimulates both cellular metabolism and mitosis. The part played by endocrine control mechanisms in the fetus is set in context by an appreciation of the importance of locally acting tissue growth factors, and in particular the somatomedins. Their part in fetal growth control is intimately bound up with the plane of nutrition experienced by the fetus. It is concluded that the simplest analysis that makes biological sense involves a consideration of hormones, tissue growth factors and nutrition, not hierarchically but as mutually interacting variables.