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Query: UNIPROT:P01275 (glucagon)
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To study the role of enteroinsular hormones in fetal macrosomia and neonatal hypoglycemia in infants of diabetic mothers, we measured plasma concentrations of free and total immunoreactive insulin, C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide at birth in 35 IDMs and 35 infants of normal mothers. Twenty fasting adults of normal weight were also studied. Sixteen IDMs were macrosomic at birth; 17 developed neonatal hypoglycemia over the first postnatal hours. The IDMs had ten times higher concentrations of free IRI than the normal infants in cord blood. Free IRI concentrations were related to the severity of maternal diabetes, with the infants of white class D to F mothers having the highest levels. The IDMs with macrosomia had a twofold increase in the concentrations of free IRI when compared with IDMs of normal weight. There was a significant correlation between the birth weight ratio and the concentrations of free IRI. The IDMs who developed neonatal hypoglycemia had considerably higher concentrations of free IRI than did normoglycemic IDMs. The decrease of blood glucose over the first postnatal hours correlated strongly with the free IRI concentrations in the cord blood. The IDMs had a threefold increase of the C-peptide concentrations over those in normal infants. Six IDMs had a molar ratio of C-peptide to free IRI of less than 1. Both the IDMs and normal infants had substantially higher concentrations of enteroglucagon and lower concentrations of GIP than did the fasting adults. Our data provide direct evidence that IDMs are markedly hyperinsulinemic at birth and that ambient hyperinsulinemia plays a crucial role in the development of fetal macrosomia and neonatal hypoglycemia. Moreover, the observed discrepancy in the relative increase of free IRI and C-peptide, combined with the low molar ratio of C-peptide to IRI, suggests a decreased metabolic clearance of insulin or transplacental passage of insulin from the maternal circulation in infants of mothers with insulin-treated diabetes.
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PMID:Relation of enteroinsular hormones at birth to macrosomia and neonatal hypoglycemia in infants of diabetic mothers. 635 86

The developing fetal endocrine pancrease produces both insulin and glucagon from an early stage in human development. These hormones do not cross the placenta and must be metabolized within the fetal-placental unit. Altered substrate metabolism in the gestational diabetic of the insulin dependent diabetic patient can pertubate normal fetal hormone homeostasis. Maternal hyperglycemia produces fetal hyperglycemia, hyperinsulinemia, and macrosomia while meticulous regulation of maternal glycemia abolishes the fetal macrosomia. Conversely, low levels of insulin or absence of fetal insulin results in fetal growth failure after 30 weeks' gestation. These examples, plus studies of the end-organ defects (receptors) in insulin metabolism, indicate that insulin is the major anabolic hormone of late fetal life. Glucagon appears to play less of a role in fetal life but has a homeostatic function in gluconeogenesis in the newborn. No specific growth-promoting role has been demonstrated for glucagon.
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PMID:Fetal endocrine pancreas. 699 31

Diabetes mellitus with its resulting derangement of various metabolic fuels, carbohydrates, amino acids, lipids, and ketones has the potential to adversely affect the developing fetus. Therefore, strict glycemic control in pregnancy has become the standard of care in modern obstetrics. A considerable amount of research has been undertaken into the metabolic changes that occur during pregnancy in both women with insulin-dependent diabetes and gestational diabetes. This paper will review current research in normal and diabetic pregnancies both in the fasting and fed states as well as during episodes of hypoglycemia. In normal pregnancy insulin secretion increases throughout gestation whereas peripheral insulin sensitivity is decreased. Fasting levels of plasma glucose are reduced by approximately 10 per cent during the first trimester. Maternal amino acid levels are also reduced in normal pregnancy, although cholesterol and triglyceride levels are increased, most dramatically in the second trimester. As gestation advances, progressively increasing amounts of insulin antagonistic hormones are secreted by the placenta. This leads to gestational diabetes in 2 to 3 per cent of women who exhibit hyperglycemia despite an increased insulin response to oral glucose as well as an increased insulin/glucagon ratio. In insulin dependent diabetes mellitus, the insulin-deficient state results in fasting and postprandial hyperaminoacidemia, hyperlipidemia, and hyperglycemia. These metabolic changes and the resulting hyperglycemic milieu can lead to fetal macrosomia that will result in maternal and fetal morbidity. Therefore, normalization of these fuels with the use of intensive insulin regimens is the goal of therapy during pregnancy.
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PMID:Metabolic changes in diabetic and nondiabetic subjects during pregnancy. 813 54