Effect of Insulin and Epinephrine on the Carbohydrate Metabolism and Adenylate Cyclase Activity of Rhesus Fetal Muscle

Bocek, Rose Mary; Young, Michal; Beatty, Clarissa H.

doi:10.1203/00006450-197310000-00001

Cited by 18 publications

(11 citation statements)

References 19 publications

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“…Experiments utilizing fetal sheep preparations have shown that insulin increases fetal glucose uptake as well as fetal glucose utilization (13,14,32,33). Studies of many animal tissues in culture, including human tissues, have demonstrated that insulin stimulates glucose uptake and protein synthesis in fetal skin, muscle, brain, adrenal, and kidney (2)(3)(4)(35)(36)(37)(38)(39)(40)(41). Since fetal pancreas exhibits none or only a limited response to acute changes in fetal blood glucose levels (12)(13)(14), the regulation of glucose metabolism in the fetus may be controlled by a hormone of extrapancreatic origin.…”

Section: Discussionmentioning

confidence: 99%

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Liu¹,

Wang²,

Mills³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Rapid growth of human fetal tissues requires insulin or insulin-like growth factors. A high rate of human fetal growth occurs between implantation and about 14 weeks of gestation. Fetal pancreatic insulin secretion begins much later. Since maternal insulin does not cross the blood/placental barrier, other sources of insulin or insulin-like growth factors may be provided for fetal development. We report here that placental polyadenylylated RNAs from the first and third trimester of normal pregnancy as well as from term pregnancies of diabetic mothers hybridize to a 32P-labeled cloned cDNA of an insulin-related sequence expressed in fetal pancreas. Moreover, placentas from diabetic women express much more of these sequences. These results suggest that insulinrelated genes are expressed in placental tissue during fetal development and may be a source of growth-promoting hormones for the human fetus. Fetuses developing in diabetic women receive a large influx of glucose. This in turn may stimulate the expression of insulin-related sequences, which may result in higher utilization of glucose, thus bringing about the macrosomia and high incidence of malformation and stillbirths known to result from pregnancies in diabetics.During the first 10 weeks of embryonic and fetal life, which is a critical period of rapid growth for the human conceptus, primary and secondary embryonic induction and organogenesis is taking place (1). Glucose is used as a major source of metabolic energy in the human fetus (2-4) and a glucose imbalance, in addition to affecting the growth of embryonic tissue, may well result in developmental abnormalities such as macrosomia, malformations, and increased rate of stillbirths, as is manifested in pregnancies of diabetic women. Insulin, a regulator of glucose metabolism, is an essential growth factor for fast-growing mammalian tissues, including human embryonic tissues (2-4); however maternal insulin does not cross the blood/placental barrier (5-8). Although it has not been established that insulin or an insulin-like growth factor is necessary for the early development of the human fetus in utero, such a requirement is not unlikely.Explants of multiple tissues from fetal mouse synthesized insulin-like somatomedin (9). The production of the insulinlike growth factors IGF-I and IGF-II is developmentally regulated, and this pattern of expression is maintained in fibroblasts derived from fetal as well as older rats (10). Receptors for insulin-like growth factors (IGF-I, IGF-II, somatomedin A, and multiplication-stimulating activity) and insulin are present in human fetal tissues at different stages of development (11). This evidence suggests that fetal growth may be regulated by insulin and/or insulin-like growth factors.The fetal pancreatic islets of Langerhans are capable of insulin synthesis only after 14 weeks of gestation, several weeks later than the critical growth period mentioned above. Further, the fetal pancreas normally exhibits only limited responses to acute changes in cord blood gl...

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Section: Discussionmentioning

confidence: 99%

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Liu¹,

Wang²,

Mills³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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“…We have demonstrated that on the basis of NCN, glu cose uptake and the rate of respiration are highest in 90-day fetal muscle, de crease with fetal development, and are lowest in adult muscle (4). The adenylate cyclase system of 100-day fetal muscle is also more sensitive to epinephrine than adult muscle (5). Although the mechanism by which prostaglandins affect cellu lar levels of cyclic AMP is not established, fetal muscle apparently is more sensitive to PGE2: greater absolute increases in cyclic AMP-14C levels were found at 100 days fetal than in the adult series.…”

Section: Discussionmentioning

confidence: 87%

“…Since cyclic AMP mediates the action of many hormones and influences a wide variety of metabolic reactions, this low level suggests that the response of adenylate cyclase in fetal tissues to hormonal stimulation is minimal. However, we have reported that cyclic AMP-i4C accumulation is about 3-fold higher in the skeletal muscle of rhesus fetuses (Macaco mulatto) at 100 days of gestation (60% of term) than in the adult and that epinephrine stimulates adenylate cyclase activity in both fetal and adult muscle; absolute increases in accumulation of 14C-cyclic AMP were about 2-fold higher in fetal than in adult muscle (5). The data for rats and rhesus monkeys appear to disagree.…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP in Developing Muscle of the Rhesus Monkey: Effect of Prostaglandin E<sub>2</sub>

Bocek¹,

Young²,

Beatty³

1976

Neonatology

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Cyclic AMP levels, measured by a competitive protein-binding assay and by a prelabeling technique with adenine-¹⁴C, were determined on fetal, infant, and adult heart, diaphragm, and skeletal muscle of the rhesus monkey (Macaca mulatta); the effect of PGE₂ on cyclic AMP accumulation was also studied. The levels of cyclic AMP were higher in the three types of muscle from 150-day fetuses (91% of term) than in adult muscles and even higher at 78–100 days fetal age, and histological evidence indicated that by 65 days gestation, the majority of the rhesus skeletal muscle cells are in the myotube stage. These data agree with the observation in cell cultures that a decrease in cyclic AMP is correlated with fusion of myoblasts to form myotubes. PGE₂ (2.8 μM) stimulated cyclic AMP accumulation in all the fetal series, even in the earliest series (47% of term), as well as in all the adult series.

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“…We have already demonstrated that the concentration of cyclic A M P is higher in fetal than in adult skeletal muscle (7,8). Since the level of A T P and F6P at all ages is such as to ensure greater inhibition of PFK, the greater PFK activity in fetal compared with adult muscle may be due to relief of this inhibition by the higher level of cyclic A M P in the fetal tissue.…”

Section: Atp MM Mm Atp T Imentioning

confidence: 99%

“…Since cyclic A M P is an active deinhibitor of fetal PFK and the level of cyclic A M P is higher in fetal than in adult skeletal muscle (7,8), we measured the relative activities of PFK in the two series under conditions (pH 8.2) which would minimize the stimulating effect of cyclic AMP. With mammalian PFK's the enzyme generally loses its susceptibility to regulation as the pH increases above 7.6 (6).…”

Section: Atp MM Mm Atp T Imentioning

confidence: 99%

Control of Glycolysis in Skeletal Muscle from Fetal Rhesus Monkeys

1976

Self Cite

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A Extractregulation of glycolysis and the action of such hormones as epinephrine there is no major difference between fetal and adult muscle. In our studies of metabolic control mechanisms in skeletal muscle from rhesus fetus we have determined the tissue levels of the metabolic intermediates and cofactors of the glycolytic pathway and During the last 15 years the scarcity of data published on the have calculated the mass-action ratios for each reaction. Skeletal and biochemistry of fetal skeletal muscle contrasts muscle from rhesus fetuses (Macaca mulatta), 90-155 days of ges-with the amount of similar information on adult muscle. Studies tational age, and from adult rhesus monkeys was used in these ex-on muscle from fetal rhesus monkeys (Macaca mulatta), which are periments.biologically similar to the human primate, are therefore of he apparent equilibrium constants for hexokinase and phospho-particular interest. Although the newborn rhesus monkey appears fructokinase (PFK) in these tissues were Over 1,000 times larger to be somewhat more advanced physically than the human baby, than the mass-action ratios at all ages studied; the corresponding we have demonstrated that rhesus skeletal muscle shows a pattern values for pyruvate kinase were more than 800 times different. of differentiation into fiber types similar to that of the adult muscle The data suggest that these three enzymes are rate-limiting for at about the same relative gestational age (73% of term) as the fetal skeletal muscle as early as 54% of gestation. The next Step human muscle (75% of term) (3). Many publications are available was to study some of the numerous factors that modify these non-on the identification of rate-limiting reactions for the glycolytic equilibrium reactions. increasing the ATP concentration had a pathway in adult skeletal and cardiac muscle (20,22), but similar marked effect on the PFK activity of both fetal and adult muscle, data on fetal muscle appear to be lacking. Experimental apfirst increasing and then inhibiting enzyme activity. At maximum proaches t~ identifying regulatory enzymes in metabolic pathways PFK activity, the amount of fructose-6-PO4 (F6P) phosphorylated include determining mass-action ratios, assaying maximal enzyme per mg of protein was 2-3 times greater in the two fetal than in activities in vitro, measuring the effects of altered flux rates on the the adult series. At a concentration of 0.3 mM, citrate decreased tissue content of pathway intermediates, measuing the rates o f PFK activity of the 100-day fetal muscle; a further decrease oc-product formation from various precursors, and investigating the curred at 1.2 mM citrate. At a citrate level of 0.3 mM, the addi-kinetic and allosteric properties of enzymes, a result of such tion of inorganic phosphate ( P I ) or cyclic A M P returned PFK ac-studies, much evidence has accrued to implicate the reactions tivity to the uninhibited levels (pH 7.0). Relief of A T P inhibition of catalyzed by hexokinase, PFK, and pyruvate kinase, as regulatory F 6 P ph...

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Effect of Insulin and Epinephrine on the Carbohydrate Metabolism and Adenylate Cyclase Activity of Rhesus Fetal Muscle

Cited by 18 publications

References 19 publications

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Insulin-related genes expressed in human placenta from normal and diabetic pregnancies.

Cyclic AMP in Developing Muscle of the Rhesus Monkey: Effect of Prostaglandin E<sub>2</sub>

Control of Glycolysis in Skeletal Muscle from Fetal Rhesus Monkeys

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