Sources and Disposition of Fetal Glucose: Studies in the Fetal Lamb

Abstract

Three aspects of fetal glucose metabolism are studied in the pregnant sheep: source of fetal glucose, rates and routes of fetal glucose disposal, and how these processes are regulated in the fetus. However, extrapolation of findings in the fetal sheep to the condition existing in the human must be made with great caution. This is mainly due to the fact that sheep are ruminants that obtain much of their energy from volatile fatty acids and fetal sheep have low glucose and high fructose concentrations.

Glycogen Phosphorylase: Developmental Expression in Rat Liver

“…In humans and other mammals late gesta tion is characterized by rapid fetal growth [ 17], This period of intrauterine life is unique in that the fetus is totally dependent upon the maternal supply of substrates for energy and growth [ 1 ]. Liver glycogen accumulates expo nentially towards term in preparation for extrautcrinc life [18,19], In temporal associa tion with this period of rapid glycogenesis in the rat, there is an exponential increase in expression of activities of the enzymes associ ated with glycogenolysis (glycogen phosphor ylase and its phosphatase) [2,18,20].…”

“…Although there is a wealth of information accumulated from metabolic studies in intact animals and in vitro, the precise molecular mechanisms involved in the regulation of fe tal glycogen metabolism have not been eluci dated [1]. It remains a puzzle why the fetal liver is so limited in its capacity for glucose production as an adaptive response to hypo glycemia.…”

“…The developing fetus is vulnerable to hypo glycemia [1], Data obtained from animal ex periments indicate that the fetus of virtually all species, including humans, has a limited capacity for glucose production when its transplacental substrate supply is compro mised [1,2]. This has potential implications, particularly for the infant of a diabetic moth er.…”

“…Because of the current practice to strive for strict maternal glycemic control with 'inten-sive insulin therapy', the mother (and thus fetus) may be at substantial risk for hypogly cemia [3]. Since the maternal capacity for endogenous glucose production is limited during hyperinsulinemia, the supply of glu cose to the fetus is likely to be compromised, leaving the fetus vulnerable to prolonged hy poglycemia [4], Since the data derived from in vivo animal experiments have failed to elucidate why the developing fetus is so vulnerable to hypogly cemia, we performed in vitro studies in the liver of the developing rat to explore one of the adaptive mechanisms leading to regula tion of fetal glucose production at the mo lecular level [1], We studied the expres sion of hepatic glycogen phosphorylase (EC 2.4.1.1), the rate-limiting enzyme for glycogenolysis which plays a pivotal role in main taining glucose homeostasis in mammalian tissues [5],…”